MARFAN SYNDROME (ONline
|
|
- Julia Hubbard
- 5 years ago
- Views:
Transcription
1 CLINICAL SCIENCES Immunohistochemical Evaluation of Conjunctival Fibrillin-1 in Marfan Syndrome Anuradha Ganesh, MD; Charles Smith, MD; Wilson Chan, MSc; Sheila Unger, MD; Nada Quercia, MSc; Maurice Godfrey, PhD; Stephen Kraft, MD; Raymond Buncic, MD; Alex Levin, MD Objective: To evaluate status of conjunctival fibrillin-1 in patients with Marfan syndrome with ectopia lentis. Methods: Frozen sections of conjunctiva from 6 patients with Marfan syndrome with ectopia lentis and from 15 age-matched control subjects were stained with mouse antihuman fibrillin-1 antibody, using an avidin biotin immunoperoxidase technique. The fibrillin-1 staining characteristics of conjunctiva were analyzed with the light microscope. Results: All the fresh frozen sections of conjunctival samples from control subjects demonstrated a characteristic pattern of fibrillin-1 staining. We observed a woven network of thin fibrils of uniform thickness surrounding collagen bundles. The fresh frozen samples from patients with Marfan syndrome showed consistent qualitative differences in fibrillin-1 staining when compared with samples from control subjects. The fibrils were longer and straighter than normal, varied in caliber, and showed fewer tendencies to form a woven pattern. Conclusions: Consistent, qualitative abnormalities in fibrillin-1 staining pattern can be seen in the conjunctiva of patients with Marfan syndrome with ectopia lentis. Conjunctival biopsy deserves further investigation as a diagnostic modality for Marfan syndrome in patients with ectopia lentis. Arch Ophthalmol. 2006;124: Author Affiliations: Department of Ophthalmology and Vision Science (Drs Ganesh, Kraft, Buncic, and Levin), Department of Pediatric Laboratory Medicine (Dr Smith and Mr Chan), Division of Clinical Genetics (Drs Unger and Levin and Ms Quercia), The Hospital for Sick Children, University of Toronto, Toronto, Ontario, and Munroe-Meyer Institute for Genetics, Nebraska Medical Center, Omaha (Dr Godfrey). Dr Ganesh is currently with Sultan Qaboos University Hospital, Muscat, Oman. MARFAN SYNDROME (ONline Mendelian Inheritance in Man [OMIM] #154700) is one of the most common inherited disorders of connective tissue with an estimated prevalence of 2 to 3 per individuals. 1 The diagnosis of Marfan syndrome is presently based on clinical evaluation and family history. 2 Although the majority of patients can be diagnosed on this basis, some patients pose a diagnostic dilemma because of variable involvement of different organ systems, considerable interfamilial and intrafamilial variability of manifestations, and many features of the condition occurring in other connective tissue disorders or in isolation. Some manifestations of Marfan syndrome are agedependent, making it difficult to apply the clinical criteria in pediatric patients. 3 The Marfan syndrome locus was mapped to chromosome 15q and the gene fibrillin-1 (FBN1) subsequently cloned. 5 A genetic linkage between isolated, autosomal-dominant ectopia lentis and the fibrillin-1 gene has also been suggested. 6,7 Linkage studies may be used to diagnose Marfan syndrome, but linkage requires many available affected and unaffected family members who are willing to undergo DNA testing. Making a DNAbased diagnosis of Marfan syndrome by identifying a FBN1 mutation is also not a trivial matter because the FBN1 gene is extremely complex, spans about 200 kilobase pairs (kbp) of genomic DNA, and has 65 exons. 8 Additionally, more than 150 mutations have been entered in the international Marfan database. 9 These have been found in almost all exons of the gene and are often specific to a family or individual. 10 Immunohistochemical staining with monoclonal antibodies confirms that fibrillin-1 is abnormal in Marfan syndrome. 11 Studies on dermal fibroblasts in culture and aortic smooth muscle cells from patients with Marfan syndrome 14 have demonstrated abnormalities in fibrillin-1. However, 35% of all patients with Marfan syndrome may display normal fibrillin-1 immunostaining patterns in skin specimens, 11 perhaps because this organ system is not always involved. Fibrillin-1 is an integral component of ocular tissues, including the conjunctiva. 15 Immunohistochemical analysis revealed differences in fibrillin-1 staining patterns in the lens capsule and zonules of patients with Marfan syndrome. 16,17 To our knowledge, the status of conjunctival fibrillin in Marfan syndrome has not been investigated. Our study was de- 205
2 Table. Clinical Features of Study Patients and Details of the FBN1 Mutation in the Marfan Group Age, y Family History Ocular Signs Cardiovascular Signs Skeletal Signs Mutation Analysis of FBN1 Gene Group 1 (Marfan)* 15 Ectopia lentis both eyes Mitral valve prolapse Mutation G A exon 23 at codon Ectopia lentis both eyes Aortic aneurysm Mutation G A exon 20 at codon Ectopia lentis both eyes Mitral valve prolapse Mutation G T exon 46 at codon Ectopia lentis both eyes Aortic root dilatation Mutation G T exon 44 at codon Ectopia lentis both eyes Aortic root dilatation Mutation C G exon 36 at codon Ectopia lentis both eyes Aortic root dilatation Mutation G A exon 36 at codon 4505 Group 2 (Control) Mean (range), 24 (8-40) Not performed Abbreviations:, present;, absent. *The mean age of the patients in group 1 was 19 years with a range of years. signed to evaluate fibrillin-1 staining in conjunctival tissue of patients with Marfan syndrome who are known to have involvement of the ocular structures by virtue of the presence of ectopia lentis. METHODS The study, conducted in 2001 through 2002, was approved by the research ethics board of The Hospital for Sick Children, Toronto, Ontario, and the Toronto Western Hospital, Toronto. Informed consent was obtained from all participants. PATIENT SELECTION Six patients with Marfan syndrome with ectopia lentis (group 1) and 15 patients who were systemically healthy and undergoing strabismus surgery (group 2) at The Hospital for Sick Children or Toronto Western Hospital were recruited for the study. The 2 study groups were age-matched (Table). Patients in group 1 were identified using the clinical records and databases of the Division of Clinical Genetics, the Ocular Genetics Program, and the health records department at The Hospital for Sick Children. Patients were selected based on availability, certainty of clinical diagnosis, presence of ectopia lentis, age old enough to comply with conjunctival biopsy when awake, and consent. The diagnosis of Marfan syndrome was ascertained through application of the Revised Berlin Criteria 2 by a consultant staff geneticist specializing in skeletal dysplasias from the Division of Clinical Genetics at The Hospital for Sick Children (S.U.) if the diagnosis had not been made by a geneticist previously. Additional diagnostic validation was obtained by performing molecular genetic (mutation) analysis on all patients with a clinical diagnosis of Marfan syndrome (M.G.). Patients in group 2 were recruited prospectively and consecutively from the practices of 2 strabismus surgeons (R.B. and S.K.). The pathologist (C.S.) reviewing the specimens was masked to the patient diagnosis. For all groups, patients were excluded from the study if they refused to give or could not give informed consent or if they had ocular conditions suspected to have potential fibrillin-1 abnormalities (chronic conjunctivitis, anterior segment dysgenesis, prior ocular surgery). Patients were excluded from group 2 if they had personal or family history or physical findings suggestive of any heritable connective tissue disorders. Among the inclusion criteria were an age older than 8 years and the ability of the patient or guardian to read and understand English. All patients had levels of visual acuity that allowed them to read the consent form. All patients were able to assent to the research even if they were not old enough to give full informed consent. Inclusion in the study was not dependent on completion of a specified follow-up. MOLECULAR GENETIC ANALYSIS Genomic DNA was extracted from peripheral blood mononuclear cells using standard techniques. The coding region of the FBN1 gene was amplified using all 65 exons, and further analysis was done using a combination of denaturing highperformance liquid chromatography and sequencing. CONJUNCTIVAL BIOPSY For group 1, conjunctival biopsy was performed in patients with Marfan syndrome under topical anesthesia. After obtaining informed consent, the surgeon excised an approximately 1 1 mm specimen from the inferior bulbar conjunctiva using toothed forceps and scissors with the patient receiving proparacaine hydrochloride 0.5%. For group 2, the control patients, conjunctival biopsy was an extension of strabismus surgery and performed at the wound margin prior to closing the conjunctival incision. All patients received a short course of topical antibiotics postoperatively and were followed up to ensure lack of complications from the procedure. 206
3 TISSUE SPECIMENS Conjunctival specimens from Marfan and strabismus patients were processed using either formalin or tissue-freezing medium. (1) Conjunctival samples from 6 patients with Marfan syndrome and 6 control subjects were fixed and embedded in neutral buffered formalin. Tissue sections with a thickness of 5 µm were placed on gelatin-coated slides and air-dried. The tissue sections were then dewaxed and rehydrated in water. (2) Conjunctival specimens from 6 patients with Marfan syndrome (same patients as formalin patients) and 9 control subjects (different from formalin patients) were embedded in a tissue-freezing medium and stored at 80 C until sectioning. Prior to immunostaining, the specimens were sectioned to a thickness of 5 µm and placed on sialynated slides. IMMUNOSTAINING The formalin-fixed paraffin sections were dewaxed in xylene and hydrated to water through a series of alcohols. The sections were then blocked with 3% hydrogen peroxide in absolute methanol for 30 minutes. The frozen section slides were fixed for 15 minutes in acetone at room temperature and washed with phosphate-buffered saline for 10 minutes. All slides were incubated at room temperature with normal horse serum (Vector Laboratory, Burlingame, Calif) to block nonspecific staining. The slides were then incubated at room temperature with mouse antihuman fibrillin-1 antibody-2 clone 12A5.18 at a 1:100 dilution (Lab Vision, Fremont, Calif) for 60 minutes in a humidity chamber. After they were washed with phosphate-buffered saline, the sections were incubated with biotinylated horse antimouse IgG (Vector Laboratory) for 30 minutes. An avidin-biotin peroxidase reagent (Vector Laboratory) was applied for 45 minutes at room temperature. After 2 phosphate-buffered saline washes, the reaction was developed in 3-3- aminobenzidine tetrahydrochloride (Sigma, St Louis, Mo) containing 0.01% hydrogen peroxide for 10 minutes. The slides were then rinsed twice in distilled water, counterstained with Harris hematoxylin, and rinsed 2 more times in distilled water. Coverslips were applied. Qualitative analysis of the fibrillin-1 staining pattern in the conjunctival samples from the 3 groups was performed by studying the samples under a light microscope. RESULTS A mutation was detected in the FBN1 gene of all patients with a clinical diagnosis of Marfan syndrome, thereby confirming the diagnosis of Marfan syndrome (Table). None of the conjunctival specimens that had been fixed in formalin stained positively for fibrillin-1. This was confirmed by repeat staining with different concentrations of the antibody and by using a new batch of the antibody. All frozen samples stained intensely for fibrillin-1. All frozen conjunctival samples from the control subjects (group 2) revealed a characteristic and reproducible pattern of fibrillin-1 staining. A woven network of thin fibrils with a consistent thickness was observed outlining many of the collagen bundles in the conjunctival stroma (Figure 1). The approximate amount of fibrillin-1 in the frozen conjunctival samples from patients with Marfan syndrome with ectopia lentis (group 1) matched that of the controls. However, consistent qualitative differences in the pattern of fibrillin-1 staining in the conjunctival stroma of all specimens A B 0.05 mm mm Figure 1. Light microscopic appearance of fibrillin-1 in conjunctival samples of control patients. A, Network of thin fibrils (arrowheads) is observed outlining the collagen bundles in the conjunctival stroma (original magnification, 40). B, The fibrillin-1 fibrils (arrowhead) are of uniform thickness (original magnification, 100; counterstain, Harris hematoxylin). were observed when compared with samples from control subjects. The fibrillin-1 fibrils were longer and slender. They showed fewer tendencies to form a meshwork (Figure 2A) and also exhibited a variation in caliber, resulting in a pattern of segmentation (Figure 2B). Morphometric analysis of fibrillin-1 could not be performed because of variability in staining of the conjunctival sections. The variation in staining was attributed to inherent variations in the thickness of sections obtained by frozen microtomy. However, on additional sections, the staining patterns confirmed the qualitative differences. COMMENT Marfan syndrome is an autosomal disorder of connective tissue that predominantly affects the cardiovascular system, musculoskeletal system, and eye. Several ocular abnormalities are found in patients with Marfan syndrome. Ectopia lentis, which occurs in up to 80% of patients with Marfan syndrome, is probably congenital in most cases and almost always bilateral. 18 Affected individuals may also present with pulmonary, dural, and skin manifestations. The diagnosis of Marfan syndrome is made when a patient satisfies the Revised Berlin Criteria. 1 Equivocal cases and pediatric patients often pose a di- 207
4 A B 0.05 mm mm Figure 2. Light microscopy showing fibrillin-1 staining pattern in conjunctival samples of patients with Marfan syndrome and ectopia lentis. A, The fibrillin-1 fibrils (arrowheads) are longer and slender when compared with control samples and show fewer tendencies to form a meshwork (original magnification, 40). B, The fibrillin-1 fibrils exhibit a variation in caliber, resulting in a pattern of segmentation and a beaded appearance (arrowhead) (original magnification, 40; counterstain, Harris hematoxylin). agnostic dilemma. Molecular diagnostic methods may be used to resolve these cases as well as define affectation in a family. However, to attain sufficient power, linkage requires families with many available affected and unaffected patients willing to undergo DNA testing. In small families and sporadic cases, which constitute up to 25% of cases, 19 linkage analysis is often not possible. Additionally, linkage studies are costly and time-consuming and may not be readily available on a clinical basis. Making a DNA-based diagnosis of Marfan syndrome by identifying a specific FBN1 mutation is also not a trivial matter because of the large and complex nature of the gene. 6 With comprehensive screening of all the exons for mutations, current techniques have a high sensitivity (66%- 100%) but a high rate of false positives (52%). 20,21 Molecular genetic analysis revealed a FBN1 mutation in all our patients with a clinical diagnosis of Marfan syndrome. These mutations are likely to be pathogenic because all of them affect cysteine residues or produce stop codons, resulting in significantly altered or truncated fibrillin-1 protein. Segregation analysis, which could confirm the pathogenicity, has not yet been performed in our patients. To our knowledge, all of the mutations we found are novel and have not been reported previously. Mutations of FBN1 in Marfan syndrome are known usually to be private. This has been attributed to the high mutation rate of the FBN1 gene and the impaired reproductive fitness of patients with Marfan syndrome due to early morbidity and mortality. 22 Fibrillin-1 is a glycoprotein that is a critical component of extracellular microfibrils and serves as a scaffold for deposition of elastin and decorin. 23 There is widespread distribution of fibrillin-1 containing microfibrils in the connective tissue matrices of the skin, lung, kidney, vasculature, cartilage, tendon, and muscle. 24 Immunohistochemical staining with monoclonal antibodies showed fibrillin-1 to be the protein that is responsible for Marfan syndrome when abnormal. 9 Microfibrillar abnormalities have been demonstrated by immunofluorescent techniques in dermal, lenticular, and cardiovascular tissues from patients with Marfan syndrome. 25 However, because of a high false-negative rate with skin biopsy and the inaccessibility of intraocular and cardiac tissue, these tissues are not desirable for diagnostic testing. 14,23 Conjunctival fibrillin-1 has not been studied in Marfan syndrome. Wheatley et al 15 reported the pattern of immunohistochemical localization of fibrillin-1 in normal ocular tissues. They observed intense staining in the conjunctival stroma for fibrillin Our study was conducted to evaluate the status of conjunctival fibrillin-1 in patients with Marfan syndrome with ectopia lentis. We are unaware of any conjunctival manifestations due to altered fibrillin-1. Further, our patients with Marfan syndrome did not have any clinically evident conjunctival disease. We hypothesized they might demonstrate altered fibrillin-1 in their conjunctiva because the ocular system is known to be involved; in contrast, the high rate of negative skin biopsies presumably relates to a lack of skin involvement in some patients. Conjunctiva is easily accessible, and conjunctival biopsy is an outpatient office procedure that can be done with most patients awake, even children, and with only a single drop of topical anesthetic. Qualitative abnormalities in fibrillin-1 immunostaining were detected in the conjunctival stroma in all of our patients with Marfan syndrome and ectopia lentis. However, fibrillin-1 staining could only be demonstrated in frozen sections of conjunctiva. Formalin fixation appears to be unsuitable for studying fibrillin-1 staining characteristics in conjunctival specimens. This may be related to the antibody used in the study (mouse antihuman fibrillin-1 antibody-2 clone 12A5.18; Lab Vision). Other fibrillin-1 antibodies might recognize fibrillin-1 in fixed tissues. Isolated, autosomal-dominant ectopia lentis may also be associated with underlying fibrillin-1 abnormalities. Fibrillin-1 protein abnormalities 10 have been demonstrated in 2 patients with isolated ectopia lentis. It is likely that some of the cases of isolated ectopia lentis represent subdiagnostic clinical variants of Marfan syndrome. Identifying these cases has potentially important implications for families because the diagnosis prompts the physician to look for other manifestations of Marfan syndrome and provide appropriate genetic counseling. Our study has indicated qualitative differences in fibrillin-1 staining pattern in the conjunctiva of patients with Marfan syndrome with ectopia lentis. Both fibrillin-1 mol- 208
5 ecules and fibrillin-rich microfibrils are susceptible to proteolytic degradation in ocular aging and disease Structural consequences of microfibrillar alterations due to aging in zonules of human lens capsules are well known, namely anterior shifting of zonular insertion onto the lens capsule and disruption of zonular bundles. 26,27 We do not believe that age was a factor in our study because our control subjects and patients with Marfan syndrome were age-matched and all younger than 40 years old. Our patients did not have other ocular surface disorders known to affect conjunctival fibrillin-1 (eg, chronic inflammation, prior surgery). Our antibody is not known to crossreact with fibrillin-2 or with other proteins. 29 The appearance of Marfan syndrome fibrillin-1 was readily identifiable by our pathologist, who was masked to patient clinical status. One limitation of our study is that we were unable to develop a quantitative technique to measure more objectively the differences between normal and Marfan fibrillin-1 staining patterns. Because this seems to be a limitation of frozen section, and because formalin fixation was unsatisfactory for fibrillin-1 analysis, we must expand our understanding of qualitative variation. To verify the results of our study and test the hypothesis that conjunctival biopsy may beanewdiagnosticmodalityformarfansyndrome, wewould require a larger sample of patients that includes patients with isolated ectopia lentis, ectopia lentis due to causes other than Marfan syndrome, and Marfan syndrome without ectopia lentis. This would perhaps allow us to define sensitivity and specificity parameters, identify age-related variations unique to Marfan syndrome, and recognize other ocular disorders that might produce false-positive results. Should our results be validated, conjunctival biopsy could be a significant advancement in the diagnosis of Marfan syndrome at a time when molecular genetic tests are unsatisfactory and clinical diagnosis at times difficult. Submitted for Publication: July 29, 2004; final revision received March 22, 2005; accepted March 26, Correspondence: Alex Levin, MD, Department of Ophthalmology, M158, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X89 (alex.levin@sickkids.ca). Financial Disclosure: None. Funding/Support: This study was supported in part by a grant from the Canadian Marfan Association, Toronto, Ontario. Previous Presentations: This study was presented in part at the annual meeting of the American Association of Pediatric Ophthalmology and Strabismus; March 22, 2002; Seattle, Wash; the 44th Annual Research Day, Department of Ophthalmology; May 17, 2002; University of Toronto, Toronto, Ontario; the annual meeting of the Canadian Ophthalmological Society; June 14, 2002; Ottawa, Ontario; and the 7th meeting of the International Society of Genetic Eye Diseases; May 19, 2003; Paris, France. Acknowledgment: We thank Professor Dr Ing. P. J. Coucke (Collagen Lab, Centrum Medische Genetica, Ghent, Belgium) for his help with the molecular genetic analyses. We thank Dr Venita Jay for her assistance in the initiation of this work. We are also grateful for the participation of our research assistants, LaToya Austin and Enza Perruzza; the Canadian Marfan Association, who provided funding; and our patients and their families. REFERENCES 1. Pyeritz RE. Marfan syndrome and other disorders of fibrillin. In: Rimoin DL, Connor JM, Pyeritz RE, eds. Principles and Practice of Medical Genetics, 3rd ed. New York, NY: Churchill Livingstone Inc; 1997: De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for Marfan syndrome. Am J Med Genet. 1996;62: Lipscomb KJ, Clayton-Smith J, Harris R. Evolving phenotype of Marfan syndrome. Arch Dis Child. 1997;76: Kainulainen K, Pulkkinen L, Savolainen A, Kaitila I, Peltonen L. Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med. 1990; 323: Dietz HC, Cutting GR, Pyeritz RE, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352: Tsipouras P, DelMastro R, Sarfarazi M, et al. Genetic linkage of the Marfan syndrome, ectopia lentis, and congenital contractural arachnodactyly to the fibrillin genes on chromosomes 15 and 5: the International Marfan Collaborative Study. N Engl J Med. 1992;326: Lonnqvist L, Child A, Kainulainen K, Davidson R, Puhakka L, Peltonen L. A novel mutation of the fibrillin gene causing ectopia lentis. Genomics. 1994;19: Biery NJ, Eldadah ZA, Moore CS, Stetten G, Spencer F, Dietz HC. Revised genomic organization of FBN1 and significance for regulated gene expression. Genomics. 1999;56: Collod-Beroud G, Beroud C, Ades L, et al. Marfandatabase (thirdedition): newmutations and new routines for the software. Nucleic Acids Res. 1998;26: Dietz HC, Pyeritz RE. Mutations in the human gene for fibrillin-1 (FBN1) in the Marfan syndrome and related disorders. Hum Mol Genet. 1995;4: Hollister DW, Godfrey M, Sakai LY, Pyeritz RE. Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N Engl J Med. 1990; 323: Aoyama T, Francke U, Gasner C, Furthmayr H. Fibrillin abnormalities and prognosis in Marfan syndrome and related disorders. Am J Med Genet. 1995;58: Kielty CM, Shuttleworth CA. Abnormal fibrillin assembly by dermal fibroblasts from 2 patients with Marfan syndrome. J Cell Biol. 1994;124: Fleischer KJ, Nousari HC, Anhalt GJ, Stone CD, Laschinger JC. Immunohistochemical abnormalities of fibrillin in cardiovascular tissues in Marfan s syndrome. Ann Thorac Surg. 1997;63: Wheatley HM, Traboulsi EI, Flowers BE, et al. Immunohistochemical localization of fibrillin in human ocular tissues. Arch Ophthalmol. 1995;113: Mir S, Wheatley HM, Hussels IE, Whittum-Hudson JA, Traboulsi EI. A comparative histologic study of the fibrillin microfibrillar system in the lens capsule of normal subjects and subjects with Marfan syndrome. Invest Ophthalmol Vis Sci. 1998;39: Traboulsi EI, Whittum-Hudson J, Mir S, Maumenee IH. Microfibril abnormalities of the lens capsule in patients with Marfan syndrome and ectopia lentis. Ophthalmic Genet. 2000;21: Cross HE, Jensen AD. Ocular complications in the Marfan syndrome and homocystinuria. Am J Ophthalmol. 1973;75: Lee B, Godfrey M, Vitale E, et al. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991;352: Matyas G, Nuytinck L, De Paepe A, Halliday D, Handford P, Steinmann S. Where is the Marfan mutation? sensitivity study of denaturing HPLC (DHPLC) for routine mutation detection in the Marfan syndrome. Presented at: EMBO course, Advanced Techniques in Molecular Medicine; August 24, 2000; Uppsala, Sweden. 21. Loeys B, Nuytinck L, Delvaux I, De Bie S, De Paepe A. Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome. Arch Intern Med. 2001;161: Robinson PN, Godfrey M. The molecular genetics of Marfan syndrome and related microfibrillopathies. J Med Genet. 2000;37: Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350 kd glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986;103: Sakai LY, Keene DR, Glanville RW, Bachinger HP. Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. J Biol Chem. 1991;266: Kielty CM, Davies SJ, Phillips JE, Jones CJ, Shuttleworth CA, Charles SJ. Marfan syndrome: fibrillin expression and microfibrillar abnormalities in a family with predominant ocular defects. J Med Genet. 1995;32: Sakabe I, Oshika T, Lim SJ, Apple DJ. Anterior shift of zonular insertion onto the anterior surface of human crystalline lens with age. Ophthalmology. 1998; 105: Hanssen E, Franc S, Garrone R. Fibrillin-rich microfibrils: structural modifications during ageing in normal human zonule. J Submicrosc Cytol Pathol. 1998; 30: Ashworth J, Kielty CM, McLeod D. Fibrillin and the eye. Br J Ophthalmol. 2000; 84: Data sheet: fibrillin-1 ab-2 (clone 12A5.18). Lab Vision Corp. Available at: http: // Accessed November 30,
UvA-DARE (Digital Academic Repository) Marfan syndrome: Getting to the root of the problem Franken, Romy. Link to publication
UvA-DARE (Digital Academic Repository) Marfan syndrome: Getting to the root of the problem Franken, Romy Link to publication Citation for published version (APA): Franken, R. (2016). Marfan syndrome: Getting
More informationOVERVIEW OF OCULAR MANAGEMENT IN MARFAN SYNDROME
OVERVIEW OF OCULAR MANAGEMENT IN MARFAN SYNDROME Prepared by: Deborah Alcorn, MD, Dianna Milewicz, MD, and Irene H Maumenee, MD OCULAR FEATURES OF MARFAN SYNDROME Marfan syndrome is a dominantly inherited
More informationEvolving phenotype of Marfan s syndrome
Archives of Disease in Childhood 1997;76:41 46 41 Evolving phenotype of Marfan s syndrome Department of Medical Genetics, St Mary s Hospital, Manchester K J Lipscomb J Clayton-Smith R Harris Correspondence
More informationMarfan s Disease in Pregnancy. A Review Of Five Recent Cases and a Consideration of Guidelines. Dr Len Kliman.
Marfan s Disease in Pregnancy A Review Of Five Recent Cases and a Consideration of Guidelines. Dr Len Kliman. Antoine Bernard-Jean Marfan (1858-1942). Son of a provincial medical practitioner who discouraged
More informationMARFANS SYNDROME-A CASE REPORT
TJPRC:International Journal of Cardiology, Echocardiography & Cardiovascular Medicine (TJPRC:IJCECM) Vol. 1, Issue 1 Jun 2015 1-6 TJPRC Pvt. Ltd. MARFANS SYNDROME-A CASE REPORT MEENA, PRAVEENA, PRIYA &
More informationSummers, Kim, West, Jennifer, Peterson, Madelyn, Stark, Denis, McGill, James J., West, Malcolm
Challenges in the diagnosis of Marfan syndrome Author Summers, Kim, West, Jennifer, Peterson, Madelyn, Stark, Denis, McGill, James J., West, Malcolm Published 2006 Journal Title Medical Journal of Australia
More informationمارفان متلازمة = syndrome Marfan Friday, 15 October :19 - Last Updated Thursday, 11 November :07
1 / 8 MARFAN SYNDROME Epidemiology Marfan syndrome is a generalized connective tissue disease affecting approximately 1 in 5000 to 10,000 individuals, with no racial, gender, or geographic predilection.
More informationARTICLE. is an autosomal dominant
ARTICLE A Recurring FBN1 Gene Mutation in Neonatal Marfan Syndrome Amanda M. Jacobs, MD; Ivanka Toudjarska, MS; Andrew Racine, MD, PhD; Petros Tsipouras, MD; Michael W. Kilpatrick, PhD; Alan Shanske, MD
More informationCorporate Medical Policy
Corporate Medical Policy Genetic Testing for Marfan Syndrome, Thoracic Aortic Aneurysms and File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_testing_for_marfan_syndrome_thoracic_aortic_aneurysms_and_dissections_and_relat
More informationUvA-DARE (Digital Academic Repository) Marfan syndrome: Getting to the root of the problem Franken, Romy. Link to publication
UvA-DARE (Digital Academic Repository) Marfan syndrome: Getting to the root of the problem Franken, Romy Link to publication Citation for published version (APA): Franken, R. (2016). Marfan syndrome: Getting
More informationProposal form for the evaluation of a genetic test for NHS Service Gene Dossier
Proposal form for the evaluation of a genetic test for NHS Service Gene Dossier Test Disease Population Triad Disease name Loeys-Dietz Syndrome OMIM number for disease 609192; 608967; 610380; 610168 Disease
More informationEffect of Angiotensine II Receptor Blocker vs. Beta Blocker on Aortic Root Growth in pediatric patients with Marfan Syndrome
Effect of Angiotensine II Receptor Blocker vs. Beta Blocker on Aortic Root Growth in pediatric patients with Marfan Syndrome Goetz Christoph Mueller University Heart Center Hamburg Paediatric Cardiology
More informationRandom Pearls in Dysmorphology and Genetics
Random Pearls in Dysmorphology and Genetics Marilyn C. Jones Professor of Clinical Pediatrics, UCSD Wellesley College, BA Columbia University P&S, MD Pediatric Residency and Fellowship in Dysmorphology,
More information강직성척추염환자에서대동맥박리를동반한마르팡증후군 1 예
대한내과학회지 : 제 84 권제 6 호 2013 Http://Dx.Doi.Org/10.3904/Kjm.2013.84.6.873 강직성척추염환자에서대동맥박리를동반한마르팡증후군 1 예 을지대학교의과대학내과학교실 류지원 박지영 송은주 허진욱 A Case of Aortic Dissection with Marfan Syndrome and Ankylosing Spondylitis
More informationInheritable Connective Tissue Diseases: Or It s Probably Not Marfan s. RJ Willes 4/23/2018
Inheritable Connective Tissue Diseases: Or It s Probably Not Marfan s RJ Willes 4/23/2018 This pretty much sums it up. Inheritable Connective tissues diseases A homogenous collection of varied syndromes
More informationMarfan syndrome affecting four generations of a family without ocular involvement
Postgrad Med J (1991) 67, 538 542 The Fellowship of Postgraduate Medicine, 1991 Marfan syndrome affecting four generations of a family without ocular involvement A.B. Bridges, M. Faed', M. Boxer', W.M.
More informationA growth disturbance and not a disorder with ligamentous laxity
Marfan Syndrome A growth disturbance and not a disorder with ligamentous laxity 1 in 5,000-10,000 extensive phenotypic variability Fibrillin-1 abnormality Chromsome no. 15 Different forms of mutations
More informationPOLYCHROMASIA CAPSULARE (MULTICOLORED CAPSULE): REPORT OF THREE FAMILIES
POLYCHROMASIA CAPSULARE (MULTICOLORED CAPSULE): REPORT OF THREE FAMILIES BY Elias I. Traboulsi MD, * Daniel Chung DO, AND John M. Koors MD ABSTRACT Purpose: To describe the familial occurrence of a peripheral
More informationHTAD PATIENT PATHWAY
HTAD PATIENT PATHWAY Strategy for Diagnosis and Initial Management of patients and families with (suspected) Heritable Thoracic Aortic Disease (HTAD) DISCLAIMER This document is an opinion statement reflecting
More informationSurgical Management of Mitral Regurgitation in Patients with Marfan Syndrome during Infancy and Early Childhood
Korean J Thorac Cardiovasc Surg 2015;48:7-12 ISSN: 2233-601X (Print) ISSN: 2093-6516 (Online) Clinical Research http://dx.doi.org/10.5090/kjtcs.2015.48.1.7 Surgical Management of Mitral Regurgitation in
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: van Seters M, van Beurden M, ten Kate FJW, et al. Treatment
More informationNIH Public Access Author Manuscript Nat Clin Pract Cardiovasc Med. Author manuscript; available in PMC 2008 October 3.
NIH Public Access Author Manuscript Published in final edited form as: Nat Clin Pract Cardiovasc Med. 2007 March ; 4(3): 167 171. doi:10.1038/ncpcardio0797. Severe aortic and arterial aneurysms associated
More informationCase Report Marfan Syndrome: A Case Report
Case Reports in Dentistry Volume 2012, Article ID 595343, 4 pages doi:10.1155/2012/595343 Case Report Marfan Syndrome: A Case Report Rajendran Ganesh, Rajendran Vijayakumar, and Haridoss Selvakumar Department
More informationProposal form for the evaluation of a genetic test for NHS Service Gene Dossier
Proposal form for the evaluation of a genetic test for NHS Service Gene Dossier Test Disease Population Triad Disease name Leber congenital amaurosis OMIM number for disease 204000 Disease alternative
More informationMarfan s Syndrome Meraj Ud Din Shah MD, DM, FICC
91 Marfan s Syndrome Meraj Ud Din Shah MD, DM, FICC Case Report: A 2 year male child was having routine check up for respiratory infection and was detected to have grade 3/6 murmur in precordium. Patient
More informationSports Participation in Patients with Inherited Diseases of the Aorta
Sports Participation in Patients with Inherited Diseases of the Aorta Yonatan Buber, MD Adult Congenital Heart Service Leviev Heart Center Safra Childrens Hospital Disclosures None Patient Presentation
More informationClinical Characteristics of Marfan Syndrome in Korea
Original Article Print ISSN 1738-5520 On-line ISSN 1738-5555 Korean Circulation Journal Clinical Characteristics of Marfan Syndrome in Korea A Young Lim, MD 1, Ju Sun Song, MD 2, Eun Kyoung Kim, MD 1,
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
Genetic Testing for Marfan Syndrome, Thoracic Aortic Page 1 of 23 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Genetic Testing for Marfan Syndrome, Thoracic Aortic
More informationInterventions of interest are: Testing for genes associated with connective tissue diseases
Genetic Testing for Marfan Syndrome, Thoracic Aortic Aneurysms (204129) Medical Benefit Effective Date: 07/01/15 Next Review Date: 05/18 Preauthorization Yes Review Dates: 05/15, 05/16, 05/17 Preauthorization
More informationGENETIC TESTING FOR MARFAN SYNDROME, THORACIC AORTIC ANEURYSMS AND DISSECTIONS AND RELATED DISORDERS
AND DISSECTIONS AND RELATED DISORDERS Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical
More informationA Case Of Marfan Syndrome With Ascending And Arch Of Aorta Aneurysm Presenting With Type A- Dissection Of Aorta.
A Case Of Marfan Syndrome With Ascending And Arch Of Aorta Aneurysm Presenting With Type A- Dissection Of Aorta. Dr E Srikanth, Dr Ravi Srinivas MD.DM, Dr O Adikesava Naidu MD.DM, FACC,FESC. Dr Y V Subba
More informationMarfan syndrome: Report of two cases with review of literature
Case Report Marfan syndrome: Report of two cases with review of literature AK Randhawa, C Mishra 1, SB Gogineni 2, S Shetty 2 Departments of Oral Medicine and Radiology, Luxmi Bai Institute of Dental Sciences
More informationCongenital Aortopathies Marfans, Loeys-Dietz, ACTA 2, etc. DATE: October 9 th, 2017 PRESENTED BY: Cristina Fuss, MD
Congenital Aortopathies Marfans, Loeys-Dietz, ACTA 2, etc. DATE: October 9 th, 2017 PRESENTED BY: Cristina Fuss, MD 24 yof present with SoB 9/4/2017 2 24yo F Presenting to local ED with SoB No other pertinent
More informationReply to The question of heterogeneity in Marfan syndrome
Reply to The question of heterogeneity in Marfan syndrome Catherine Boileau, Claudine Junien, Gwenaëlle Collod, Guillaume Jondeau, Olivier Dubourg, Jean-Pierre Bourdarias, Catherine Bonaïti-Pellié, Jean
More informationCLINICAL INFORMATION SHEET
CLINICAL INFORMATION SHEET Marfan syndrome and related aortic aneurysm syndromes Patient information Name: First Name(s): Sex: M F Date of Birth (dd/mm/yyyy): / / Address: Referring Physician: Referring
More informationMarfan syndrome in the third Millennium Collod-Béroud
Author manuscript, published in "European Journal of Human Genetics 2002;10(11):673-81" DOI : 10.1038/sj.ejhg.5200876 Marfan syndrome in the third Millennium Collod-Béroud 1 Gwenaëlle *, Boileau Catherine
More informationProposal form for the evaluation of a genetic test for NHS Service Gene Dossier
Proposal form for the evaluation of a genetic test for NHS Service Gene Dossier Test Disease Population Triad Disease name Choroideremia OMIM number for disease 303100 Disease alternative names please
More informationCURRENT UNDERSTANDING: ANATOMY & PHYSIOLOGY TYPE B AORTIC DISSECTION ANATOMY ANATOMY. Medial degeneration characterized by
DISCLOSURES CURRENT UNDERSTANDING: INDIVIDUAL None & PHYSIOLOGY TYPE B AORTIC DISSECTION INSTITUTIONAL Cook, Inc Not discussing off-label use of anything Medial degeneration characterized by Smooth muscle
More informationMarfan syndrome: diagnosis and management. JCS Dean Consultant and Honorary Reader, Department of Medical Genetics, Medical School, Aberdeen, Scotland
PAPER 2007 Royal College of Physicians of Edinburgh Consultant and Honorary Reader, Department of Medical Genetics, Medical School, Aberdeen, Scotland ABSTRACTThe diagnosis of Marfan syndrome requires
More informationZytoFast CMV Probe (Biotin-labeled)
ZytoFast CMV Probe (Biotin-labeled) T-1013-400 40 (0.4 ml) For the detection of Cytomegalovirus (CMV) DNA by chromogenic in situ hybridization (CISH).... For Research Use Only. Not for use in diagnostic
More informationFamilial Arteriopathies
Familial Arteriopathies Reed E. Pyeritz, MD, PhD Perelman School of Medicine University of Pennsylvania Longest and largest blood vessel Anatomical segments differ in physiologic function, embryonic origins
More informationTITLE: The Role of hcdc4 as a Tumor Suppressor Gene in Genomic Instability Underlying Prostate Cancer
AD Award Number: TITLE: The Role of hcdc4 as a Tumor Suppressor Gene in Genomic Instability Underlying Prostate Cancer PRINCIPAL INVESTIGATOR: Audrey van Drogen, Ph.D. CONTRACTING ORGANIZATION: Sidney
More informationThe Prevalence of Marfan Syndrome in Korea
ORIGINAL ARTICLE Epidemiology, Occupation & Environmental Medicine https://doi.org/.6/jkms.7...76 J Korean Med Sci 7; : 76-8 The of Marfan Syndrome in Korea Shin Yi Jang, Su Ra Seo, Seung Woo Park, and
More informationFamilial aggregation studies indicate that up to 20% of
Mapping a Locus for Familial Thoracic Aortic Aneurysms and Dissections (TAAD2) to 3p24 25 Sumera N. Hasham, PhD; Marcia C. Willing, MD, PhD; Dong-chuan Guo, PhD; Ann Muilenburg, MA; Rumin He, MD; Van T.
More informationVASCULITIS AND VASCULOPATHY
VASCULITIS AND VASCULOPATHY Mantosh S. Rattan @CincyKidsRad facebook.com/cincykidsrad Disclosure No relevant financial disclosures Outline Overview Referral pathways MR imaging Case examples Vasculitis
More informationProtocols. Harvesting and Sectioning the Ascending Aorta
DAUGHERTY LAB Saha Cardiovascular Research Center University of Kentucky Protocols Harvesting and Sectioning the Ascending Aorta Page 1 of 7 Harvesting the ascending aorta Materials: 1. Insulin syringe
More information22q11.2 DELETION SYNDROME. Anna Mª Cueto González Clinical Geneticist Programa de Medicina Molecular y Genética Hospital Vall d Hebrón (Barcelona)
22q11.2 DELETION SYNDROME Anna Mª Cueto González Clinical Geneticist Programa de Medicina Molecular y Genética Hospital Vall d Hebrón (Barcelona) Genomic disorders GENOMICS DISORDERS refers to those diseases
More informationNeutrophils contribute to fracture healing by synthesizing fibronectin+ extracellular matrix rapidly after injury
Neutrophils contribute to fracture healing by synthesizing fibronectin+ extracellular matrix rapidly after injury Bastian OW, Koenderman L, Alblas J, Leenen LPH, Blokhuis TJ. Neutrophils contribute to
More informationCURRENT GENETIC TESTING TOOLS IN NEONATAL MEDICINE. Dr. Bahar Naghavi
2 CURRENT GENETIC TESTING TOOLS IN NEONATAL MEDICINE Dr. Bahar Naghavi Assistant professor of Basic Science Department, Shahid Beheshti University of Medical Sciences, Tehran,Iran 3 Introduction Over 4000
More informationAortopathy Gene Testing by Sanger sequencing
Department of Molecular Genetics Aortopathy Gene Testing by Sanger sequencing Mutation screening for Marfan syndrome and related disorders has grown to include many genes with overlapping phenotypes. We
More informationclinical diagnostic criteria for this disorder have been established, 3 4 the latest being the Ghent criteria, which superseded
ARTICLE Effect of Mutation Type and Location on Clinical Outcome in 1,013 Probands with Marfan Syndrome or Related Phenotypes and FBN1 Mutations: An International Study L. Faivre, G. Collod-Beroud, B.
More informationMP Genetic Testing for Marfan Syndrome, Thoracic Aortic Aneurysms and Dissections, and Related Disorders. Related Policies None
Medical Policy Genetic Testing for Marfan Syndrome, Thoracic Aortic Aneurysms and Dissections, and Related Disorders BCBSA Ref. Policy: 2.04.129 Last Review: 02/21/2019 Effective Date: 02/21/2019 Section:
More informationProposal form for the evaluation of a genetic test for NHS Service Gene Dossier
Proposal form for the evaluation of a genetic test for NHS Service Gene Dossier Test Disease Population Triad Disease name and description (please provide any alternative names you wish listed) (A)-Testing
More informationOriginal Research Article
STUDY OF EPITHELIAL PHENOTYPE AFTER PTERYGIUM EXCISION BY USING CONJUNCTIVAL IMPRESSION CYTOLOGY. Dr. Sachin O. Agrawal*, Dr. Sudhir Pendke, Dr. Ravi Chauhan Department of Ophthalmology, Indira Gandhi
More informationGENETICS 101. An overview of human genetics and practical applications from an adult medical genetics clinic
GENETICS 101 An overview of human genetics and practical applications from an adult medical genetics clinic Historical timeline of genetics Discuss basics of genetics Discuss tools used in clinic Discuss
More informationInterpretation Manual - Gastric or Gastroesophageal Junction Adenocarcinoma. PD-L1 IHC 22C3 pharmdx is FDA-approved for in vitro diagnostic use
Interpretation Manual - Gastric or Gastroesophageal Junction Adenocarcinoma PD-L1 IHC 22C3 pharmdx is FDA-approved for in vitro diagnostic use For countries outside of the United States, see the local
More informationGenetic Testing for Heritable Disorders of Connective Tissue
Medical Policy Manual Genetic Testing, Policy No. 77 Genetic Testing for Heritable Disorders of Connective Tissue Next Review: June 2019 Last Review: June 2018 Effective: July 1, 2018 IMPORTANT REMINDER
More informationCitation Acta Medica Nagasakiensia. 1992, 37
NAOSITE: Nagasaki University's Ac Title Author(s) A Study on the Expression of EGFR a Content in the Stomach Cancer Tissu Nakazaki Takayuki Citation Acta Medica Nagasakiensia. 1992 37 Issue Date 1992-12-25
More informationEvaluation of the diagnostic value of immunocytochemistry and in situ hybridization in the pediatric leprosy
Indian J Lepr 203, 85 : 93- Hind Kusht Nivaran Sangh, New Delhi http://www.ijl.org.in Original Article Evaluation of the diagnostic value of immunocytochemistry and in situ hybridization in the pediatric
More informationNatural history of cardiovascular manifestations in Marfan syndrome
Arch Dis Child 01;84:129 137 129 Department of Paediatrics H3-0, Emma Children s Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, AZ Amsterdam, Netherlands CDMvanKarnebeek MSJNaeV
More informationDiseases of the aorta: Pediatric and adult clinical presentation of the main syndromes. Birgit Donner Universitäts-Kinderspital beider Basel
Diseases of the aorta: Pediatric and adult clinical presentation of the main syndromes Birgit Donner Universitäts-Kinderspital beider Basel Seite 2 Pubmed Results >10.000 publications/10 yrs Seite 3 Which
More informationPathophysiology. Tutorial 1 Genetic Diseases
Pathophysiology Tutorial 1 Genetic Diseases ILOs Analyze genetic pedigrees and recognize the mode of inheritance of diseases. Differentiate between patterns of inheritance based on the type of the protein
More informationEvaluation of Serosal Nerves in Hirschsprung Disease
Evaluation of Serosal Nerves in Hirschsprung Disease Mudassira and Anwar ul Haque Department of Pathology, Pakistan Institute of Medical Sciences, Islamabad. Introduction: For the diagnosis of Hirschsprung
More informationNIH Public Access Author Manuscript Cell Struct Funct. Author manuscript; available in PMC 2011 March 10.
NIH Public Access Author Manuscript Published in final edited form as: Cell Struct Funct. 2000 April ; 25(2): 69 72. Elastic and Collagenous Networks in Vascular Diseases Emilio Arteaga-Solis, Barbara
More informationIndex. derm.theclinics.com. Note: Page numbers of article titles are in boldface type.
Note: Page numbers of article titles are in boldface type. A Adhesion and migration, the diverse functions of the laminin a3 subunit, 79 87 Alopecia in epidermolysis bullosa, 165 169 Amblyopia and inherited
More informationIdiopathic Bronchiectasis and Connective Tissue Fibrillinopathies: Dural Ectasia as a Marker of a Distinct Bronchiectasis Subgroup
Idiopathic Bronchiectasis and Connective Tissue Fibrillinopathies: Dural Ectasia as a Marker of a Distinct Bronchiectasis Subgroup M. Leigh Anne Daniels, MD, MPH University of North Carolina October 2,
More informationThe new Ghent criteria for Marfan syndrome: what do they change?
The new Ghent criteria for Marfan syndrome: what do they change? G Faivre, Gwenaëlle Collod-Béroud, A Adès, A Arbustini, C Child, C Callewaert, B Loeys, C. Binquet, G Gautier, M. Mayer, et al. To cite
More informationUvA-DARE (Digital Academic Repository) Marfan syndrome: Getting to the root of the problem Franken, Romy. Link to publication
UvA-DARE (Digital Academic Repository) Marfan syndrome: Getting to the root of the problem Franken, Romy Link to publication Citation for published version (APA): Franken, R. (2016). Marfan syndrome: Getting
More informationDirect immunofluorescence of skin using formalin-fixed paraffin-embedded sections
Direct immunofluorescence of skin using formalin-fixed paraffin-embedded sections SL MERA, EW YOUNG, AND JWB BRADFIELD J Clin Pathol 1980; 33: 365-369 From the University Department ofpathology, University
More informationCornea with Peters Anomaly: Perturbed Differentiation of Corneal Cells and Abnormal Extracellular Matrix in the Corneal Stroma
LABORATORY INVESTIGATION Cornea with Peters Anomaly: Perturbed Differentiation of Corneal Cells and Abnormal Extracellular Matrix in the Corneal Stroma Kiyomi Ohkawa*, Shizuya Saika*, Yuko Hayashi*, Akihiko
More informationCase report. Open Access. Abstract
Open Access Case report Late diagnosis of Marfan syndrome with fatal outcome in a young male patient: a case report Aurora Bakalli 1 *, Tefik Bekteshi 1, Merita Basha 2, Afrim Gashi 3, Afërdita Bakalli
More informationCells and viruses. Human isolates (A/Kawasaki/173/01 [H1N1], A/Yokohama/2057/03 [H3N2],
Supplementary information Methods Cells and viruses. Human isolates (A/Kawasaki/173/01 [H1N1], A/Yokohama/2057/03 [H3N2], and A/Hong Kong/213/03 [H5N1]) were grown in Madin-Darby canine kidney (MDCK) cells
More informationSyndrome of the month
_t Med Genet 1996;33:403-408 Syndrome of the month 403 Marfan syndrome Jonathon R Gray, Sarah J Davies It is almost a century since Dr Antoine Bernard Marfan (1858-1942) presented Gabrielle P to the Medical
More informationNew Insights on Genetic Aspects of Thoracic Aortic Disease
New Insights on Genetic Aspects of Thoracic Aortic Disease John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Director, Aortic Institute at Yale-New Haven Yale University School of Medicine
More informationIntrascleral-fixated intraocular lenses for aphakic correction in the absence of capsular support
European Journal of Ophthalmology / Vol. 17 no. 5, 2007 / pp. 714-719 Intrascleral-fixated intraocular lenses for aphakic correction in the absence of capsular support R.A. AZNABAYEV, I.S. ZAIDULLIN, M.S.H.
More informationThoracic Aortic Aneurysms with a Genetic Basis
Thoracic Aortic Aneurysms with a Genetic Basis Aws Hamid 1, Elizabeth Lee 1, Maryam Ghadimi Mahani 1, Brian Smiley 1, Jimmy C Lu 1,2, Adam L Dorfman 1,2, Prachi P Agarwal 1 Department of Radiology, University
More informationLIST OF ORGANS FOR HISTOPATHOLOGICAL ANALYSIS:!! Neural!!!!!!Respiratory:! Brain : Cerebrum,!!! Lungs and trachea! Olfactory, Cerebellum!!!!Other:!
LIST OF ORGANS FOR HISTOPATHOLOGICAL ANALYSIS:!! Neural!!!!!!Respiratory:! Brain : Cerebrum,!!! Lungs and trachea! Olfactory, Cerebellum!!!!Other:! Spinal cord and peripheral nerves! Eyes, Inner ear, nasal
More informationIKKα Causes Chromatin Modification on Pro-Inflammatory Genes by Cigarette Smoke in Mouse Lung
IKKα Causes Chromatin Modification on Pro-Inflammatory Genes by Cigarette Smoke in Mouse Lung Se-Ran Yang, Samantha Valvo, Hongwei Yao, Aruna Kode, Saravanan Rajendrasozhan, Indika Edirisinghe, Samuel
More informationPreanalytic Variables in Cytology: Lessons Learned from Next Generation Sequencing
@Sinchita_Roy #USCAP2017 #PulmPath #IAmUSCAP #insitupathologists Preanalytic Variables in Cytology: Lessons Learned from Next Generation Sequencing Sinchita Roy-Chowdhuri, MD, PhD Department of Pathology
More informationSUPPLEMENTARY MATERIAL. Sample preparation for light microscopy
SUPPLEMENTARY MATERIAL Sample preparation for light microscopy To characterize the granulocytes and melanomacrophage centers, cross sections were prepared for light microscopy, as described in Material
More informationDistribution of type IV collagen, laminin, nidogen and fibronectin in the haemodynamically stressed vascular wall
Histol Histopath (1 990) 5: 161-1 67 Histology and Histopathology Distribution of type IV collagen, laminin, nidogen and fibronectin in the haemodynamically stressed vascular wall Reinhold Kittelberger,
More informationDiagnosis of thoracic endometriosis with immunohistochemistry
Original Article Diagnosis of thoracic endometriosis with immunohistochemistry Yo Kawaguchi 1,2, Jun Hanaoka 1, Yasuhiko Ohshio 1, Tomoyuki Igarashi 1, Keigo Okamoto 1, Ryosuke Kaku 1, Kazuki Hayashi 1,
More informationUniversity of Groningen. Marfan syndrome and related connective tissue disorders Aalberts, Jan
University of Groningen Marfan syndrome and related connective tissue disorders Aalberts, Jan IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
More informationLikes ML, Johnston TA. Gastric pseudoaneurysm in the setting of Loey s Dietz Syndrome. Images Paediatr Cardiol. 2012;14(3):1-5
IMAGES in PAEDIATRIC CARDIOLOGY Likes ML, Johnston TA. Gastric pseudoaneurysm in the setting of Loey s Dietz Syndrome. Images Paediatr Cardiol. 2012;14(3):1-5 University of Washington, Pediatrics, Seattle
More informationAn aneurysm is a localized abnormal dilation of a blood vessel or the heart Types: 1-"true" aneurysm it involves all three layers of the arterial
An aneurysm is a localized abnormal dilation of a blood vessel or the heart Types: 1-"true" aneurysm it involves all three layers of the arterial wall (intima, media, and adventitia) or the attenuated
More informationProposal form for the evaluation of a genetic test for NHS Service Gene Dossier
Proposal form for the evaluation of a genetic test for NHS Service Gene Dossier Test Disease Population Triad Disease name and description (please provide any alternative names Osteogenesis Imperfecta
More informationSheet #9. Dr. Heba Kalbouneh. Dr. Heba Kalbouneh. Dr. Heba Kalbouneh
Sheet #9 Dr. Heba Kalbouneh Dr. Heba Kalbouneh Dr. Heba Kalbouneh Elastic fibers The main function of elastic fibers is to provide elasticity. In other words these fibers are able to restore the original
More informationCase Report Bilateral Crystalinian Ectopia Surgery In The Marfan's Disease In A 16-Year Child
IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-issn: 2279-0853, p-issn: 2279-0861.Volume 17, Issue 9 Ver. 12 (September. 2018), PP 42-46 www.iosrjournals.org Case Report Bilateral Crystalinian
More informationContributions to Anatomic Pathology, over the years
Contributions to Anatomic Pathology, over the years Anatomic Pathology, part 1 G.B. Morgagni Xavier Bichat Rudolf Wirchow Anatomic Pathology, part 1 Anatomic pathology materials: morphological samples
More informationOriginal Article. Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan Syndrome
Original Article Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan Syndrome Romy Franken, MD; Alexander W. den Hartog, MD; Teodora Radonic, MD, PhD; Dimitra Micha, PhD;
More informationAscending aorta dilation and aortic valve disease : mechanism and progression
Ascending aorta dilation and aortic valve disease : mechanism and progression Agnès Pasquet, MD, PhD Pôle de Recherche Cardiovasculaire Institut de Recherche Expérimentale et Clinique Université catholique
More informationAppendix 1. A. Procedure for preparing histopathology slides. The liver removed and stored immediately in buffered formalin 10 % for
Appendix 1 A. Procedure for preparing histopathology slides. The liver removed and stored immediately in buffered formalin 10 % for histopathological examination. The tissue fixed for at least 48 hours
More informationCover Page. The handle holds various files of this Leiden University dissertation.
Cover Page The handle http://hdl.handle.net/887/20926 holds various files of this Leiden University dissertation. Author: Hilhorst-Hofstee, Yvonne Title: Clinical and genetic aspects of Marfan syndrome
More informationAMERICAN ACADEMY OF PEDIATRICS. Health Supervision for Children With Marfan Syndrome
AMERICAN ACADEMY OF PEDIATRICS Health Supervision for Children With Marfan Syndrome Committee on Genetics ABSTRACT. This set of guidelines is designed to assist the pediatrician in caring for children
More informationMost mammalian cells are located in tissues where they are surrounded by a complex extracellular matrix (ECM) often referred to as connective tissue.
GLYCOSAMINOGLYCANS Most mammalian cells are located in tissues where they are surrounded by a complex extracellular matrix (ECM) often referred to as connective tissue. The ECM contains three major classes
More informationEarly Surgical Experience With Loeys-Dietz: A New Syndrome of Aggressive Thoracic Aortic Aneurysm Disease
Early Surgical Experience With Loeys-Dietz: A New Syndrome of Aggressive Thoracic Aortic Aneurysm Disease Jason A. Williams, MD, Bart L. Loeys, MD, Lois U. Nwakanma, MD, Harry C. Dietz, MD, Philip J. Spevak,
More informationAmong the benign intraepithelial melanocytic proliferations, Inflamed Conjunctival Nevi. Histopathological Criteria. Resident Short Reviews
Resident Short Reviews Inflamed conjunctival nevi (ICN) may suggest malignancy because of their rapid growth and atypical histology. The objective of this study was to characterize the diagnostic features
More informationExplain the laboratory diagnosis of Rabies?
Explain the laboratory diagnosis of Rabies? The standard test for rabies testing is dfa. This test has been thoroughly evaluated for more than 40 years, and is recognized as the most rapid and reliable
More informationIHC Polymer. BioGenex Website. Presented for: Presented by: Date: BioGenex Tech Support 2016
IHC Polymer Presented for: Presented by: Date: BioGenex Website BioGenex Tech Support 2016 Immunohistochemistry (IHC) Quick Guide# Super SensitiveTM Polymer-HRP kits. Baking An-gen Retrieval DeWax Overnight,
More information