Clinical Spectrum and Genetic Mechanism of GLUT1-DS. Yasushi ITO (Tokyo Women s Medical University, Japan)
|
|
- Lindsay Parrish
- 5 years ago
- Views:
Transcription
1 Clinical Spectrum and Genetic Mechanism of GLUT1-DS Yasushi ITO (Tokyo Women s Medical University, Japan)
2 Glucose transporter type 1 (GLUT1) deficiency syndrome Mutation in the SLC2A1 / GLUT1 gene Deficiency of GLUT1 protein Impaired Glucose transport into the brain Failure of Energy production in the brain Impaired Brain functions (Metabolic Encephalopathy)
3 GLUT1 deficiency syndrome is characterized by l early-onset Epilepsy Paroxysmal abnormal eye movement, l subsequent Developmental delay, Paroxysmal / Static spasticity, ataxia, and dystonia, Other paroxysmal phenomena.
4 Phenotypic Spectrum of GLUT1-DS Mullen et al, 2010 Paroxysmal Exerciseinduced Dyskinesia Movement Disorder Epilepsy Idiopathic Generalized Epilepsy (IGE) Mild Mild Ataxia Epilepsy and Movement Disorder Focal Epilepsy Pharmacoresistant IGE Complex Movement Disorders with a combination of Ataxia, Spasticity, and Dystonia GLUT1 Encephalopathy Myoclonic- Astatic Epilepsy Intractable Infantile Seizures Severe Severe
5 Broad Clinical Spectrum of GLUT1-DS l Paroxysmal exercise-induced dyskinesia (PED) l Early-onset absence epilepsy (EOAE) l Myoclonic astatic epilepsy (MAE) l Alternating hemiplegia of childhood (AHC) l Dystonic tremor l Hemolytic anemia with Hereditary stomatocytoses
6 Phenotypic Spectrum of GLUT1-DS based on the hypothetical Residual GLUT1 Function in the Blood-Brain Barrier Wang et al, 2005 Phenotype Residual function Minimal % Mild Moderate (Classic) Severe Embryonic lethal Mutation / Remarks l heterozygous Missense mutation l triggered by Environmental factors that inhibit GLUT1 transport activity 50-75% l heterozygous Missense mutation 50% l hemizygote; Large deletion, Nonsense, Frameshift, and Splice-site mutation 25-50% l compound heterozygous mutation 0-25% l homozygous mutation
7 Relations between Genotype and Phenotype in GLUT1-DS patients Leen et al, 2010 Type A (n=21) B (n=30) C (n=6) Mutation Missense Nonsense, Frame shift, Splice site, or translation inhibition Multiple exon deletion Mild Mental Retardation 79% 26% Movement Disorders 63% 88% Early-onset Classical Phenotype 52% 63% 100% Non-Classical Phenotype 20% 14% 0%
8 Hereditary Pattern of GLUT1-DS l GLUT1-DS transmission is mostly sporadic, but several familial cases have also been reported. l Familial GLUT1-DS is mainly inherited in an autosomal dominant manner, but there are rare cases of autosomal recessive inheritance or parental mosaicism.
9 Activities of Daily Living (ADL) in Patients with GLUT1-DS A nationwide survey of GLUT1-DS in Japan (Male 23; Female 23: 3-35 yrs) Bathing Grooming Toile0ng Locomo0on Dressing Feeding Independence Preparing Watching Par0al assistance Total assistance 0% 20% 40% 60% 80% 100% 15% of patients needed total assistance to perform ADL, 30% needed partial assistance in all ADL except for eating, but 40% patients lead an independent life.
10 A Japanese Family Case with GLUT1-DS caused by S324L mutation in SLC2A1 Normal mentality, Infant-onset, pharmacosensitive partial epilepsy index case Mild mental retardation, Infant-onset, pharmacosensitive partial epilepsy, PED Mild ataxia 42y Case 2 16y 5y 3y Case 1 Case 3 Case 4 Borderline mentality, Infant-onset, pharmacosensitive generalized epilepsy, Adult-onset paroxysmal dystonia Moderate developmntal delay, No epilepsy
11 Clinical Summary of previously reported 15 Families with Autosomal dominant GLUT1-DS Family No. Anticipation of Mutation Age Phenotype Accel- Severity of eration ranges of Age Amino-acid Type (years) MR Epi PED Others MR Epi Sympt oms at onset PED in Upper Generation Reduced Penetrance 1 S324L Missence 3 to 42 ± ~ Ataxia +? ) 2 G91D Missence 10 to 46 + ~ Ataxia, Spascity + + +? 6) 7) 3 R126H Missence 8 to 78 - ~ Ataxia ) 8) 4 R126C Missence 1 & 31 ND + - Apnea, Abnormal eye movement ND ND +? 9) 5 G314S Missence 19 to 67 - ~ ? ) 10) 6 A275T Missence 7 to 44? - + Dystonia, Chorea? ) 7 S95I Missence 5 to 70 - ~ ?? ) 11) 8 R126C Missence 13 & Ataxia - - +? 2) 9 R93W Missence 10 &? - ~ Chorea + - +? 2) 10 S324L Missence 28 to 83 - ~ ± + + Ataxia + +? ) 12) 11 R223P Missence 22 to ? ) 12) 12 M344T Missence 14 &? + ~ Ataxia ) 13 c.18+1g>a Splice site 5 &? - ~ ) 14 c.746del; ins9 Deletion/ Insertion 15 Q282_S285del Deletion 9 to 60 - ~ & 16 + ~ Ataxia 2) Ref. No Hemolytic anemia ) 10) +, present; -, absent?, unclear; ND, not described; +++, severe MR; ++, moderate MR; +, mild MR: ±, bordeline mentality; -, normal mentality; MR, mental retardation; Epi, epilepsy; PED, paroxysmal exercise-induced dyskinesia.
12 Autosomal Recessive Familial GLUT1-DS % of 3-OMG RBC glucose uptake compared to an intra-assay control sample Family 1 Fa1 Mo1 Fa2 Mo2 87% Cousin 83% 84% Family 2 Pa2 66% Pa3 63% 52% ±8.94 Rotstein et al, 2010 Pa1 Phenotype Normal 36% Minimal / Mild Moderate / Classic Severe Embryonic lethal de novo mutation in the paternally derived allele
13 The GLUT1 Protein Transmembrane Configuration with the Locations of the R126L, K256V and R468W missense mutations Family 1 Family 2 Fa1 Mo1 Pa1 Fa2 Mo2 Pa2 Pa3 R126L ー / ー ー / ー +/ ー ー / ー ー / ー ー / ー ー / ー K256V ー / ー ー /+ +/+ ー / ー ー / ー ー / ー ー / ー R468W ー / ー ー /+ +/+ ー /+ ー /+ +/+ +/+ Uptake 100% 87% 36% 83% 84% 66% 63% Phenotype Healthy Healthy Severe Healthy Healthy Mild Minimal
14 The Brain Glucose Demands in Normal Children Fetus 3 to 4 yrs 10 s Adulthood
15 SUMMARY l In GLUT1-DS, there are variations in clinical phenotype and severity due to differences in gene mutations and residual function of GLUT1 protein. l Additionally, heterogeneity in clinical phenotype and severity is present not only among unrelated patients but also among patients within a family bearing the same autosomal dominant mutation. l The glucose demands of the brain vary with age. There are also agedependent differences in the symptoms. l Familial cases of GLUT1-DS may manifest asymptomatic to mild phenotypes in terms of intellectual disability and/or epilepsy in early generations, whereas more severe phenotypes and earlier onset ages appear in the next generations, showing an anticipation phenomenon. l Therefore, the mechanism of GLUT1-DS pathogenesis appears to be highly complex.
variant led to a premature stop codon p.k316* which resulted in nonsense-mediated mrna decay. Although the exact function of the C19L1 is still
157 Neurological disorders primarily affect and impair the functioning of the brain and/or neurological system. Structural, electrical or metabolic abnormalities in the brain or neurological system can
More informationObjectives. Genetics and Rett syndrome: As easy as apple pie! Chromosome to gene to protein
Genetics and Rett syndrome: As easy as apple pie! Victoria Mok Siu M.D., FRCPC, FCCMG ORSA conference Ottawa April 24, 2016 Objectives Review chromosomes and genes Understand s Explore the reasons behind
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 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 Epileptic encephalopathy, early infantile 4. OMIM number for disease 612164 Disease
More informationKetogenic Diet therapy in Myoclonic-Atonic Epilepsy (MAE)
KD therapy in epilepsy syndromes Ketogenic Diet therapy in Myoclonic-Atonic Epilepsy (MAE) Hirokazu Oguni, MD Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan Epilepsy Center, TMG
More informationProf. dr Michèl A. Willemsen. Radboud university medical center Department of Pediatric Neurology Nijmegen, The Netherlands Milano, Oct 2016
GLUT1DS and CSF Prof. dr Michèl A. Willemsen Radboud university medical center Department of Pediatric Neurology Nijmegen, The Netherlands Milano, Oct 2016 Content GLUT1DS diagnosis: the central role
More informationSingle Gene (Monogenic) Disorders. Mendelian Inheritance: Definitions. Mendelian Inheritance: Definitions
Single Gene (Monogenic) Disorders Mendelian Inheritance: Definitions A genetic locus is a specific position or location on a chromosome. Frequently, locus is used to refer to a specific gene. Alleles are
More informationJULY 21, Genetics 101: SCN1A. Katie Angione, MS CGC Certified Genetic Counselor CHCO Neurology
JULY 21, 2018 Genetics 101: SCN1A Katie Angione, MS CGC Certified Genetic Counselor CHCO Neurology Disclosures: I have no financial interests or relationships to disclose. Objectives 1. Review genetic
More informationProduct Description SALSA MLPA Probemix P138-C1 SLC2A1-STXBP1 To be used with the MLPA General Protocol.
Product Description SALSA Probemix P138-C1 SLC2A1-STXBP1 To be used with the MLPA General Protocol. Version C1. For complete product history see page 7. Catalogue numbers: P138-025R: SALSA MLPA probemix
More informationGENOTYPE-PHENOTYPE CORRELATIONS IN GALACTOSEMIA COMPLICATIONS COMPLICATIONS COMPLICATIONS LONG-TERM CHRONIC COMPLICATIONS WITH NO CLEAR CAUSE
Galactosemia Deficiency: galactose-1-phosphate-uridyltransferase(galt) GENOTYPE-PHENOTYPE CORRELATIONS IN GALACTOSEMIA GALT D-galactose-1-phosphate UDPgalactose + + UDPglucose D-glucose-1-phosphate DIVISION
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 informationGenetics of Hereditary Spastic Paraplegia Dr. Arianna Tucci
Genetics of Hereditary Spastic Paraplegia 1 Clinical Research Fellow Institute of Neurology University College London Hereditary spastic paraplegia: definition Clinical designation for neurologic syndromes
More informationBasic Definitions. Dr. Mohammed Hussein Assi MBChB MSc DCH (UK) MRCPCH
Basic Definitions Chromosomes There are two types of chromosomes: autosomes (1-22) and sex chromosomes (X & Y). Humans are composed of two groups of cells: Gametes. Ova and sperm cells, which are haploid,
More informationfor a bright reaching resources
resources e Glut1 Deficiency Foundation is a non-profit family organization dedicated to improving the lives of those in the Glut1 Deficiency community through its mission of: increased awareness improved
More informationComputational Systems Biology: Biology X
Bud Mishra Room 1002, 715 Broadway, Courant Institute, NYU, New York, USA L#4:(October-0-4-2010) Cancer and Signals 1 2 1 2 Evidence in Favor Somatic mutations, Aneuploidy, Copy-number changes and LOH
More informationCase presentations from diagnostic exome sequencing results in ion channels M. Koko, U. Hedrich, H. Lerche DASNE meeting 2017, Eisenach
Case presentations from diagnostic exome sequencing results in ion channels M. Koko, U. Hedrich, H. Lerche DASNE meeting 2017, Eisenach CASE 1: Clinical picture Patient s presentation: 38 year old jewish
More informationHuman Genetic Disorders
Human Genetic Disorders HOMOLOGOUS CHROMOSOMES Human somatic cells have 23 pairs of homologous chromosomes 23 are inherited from the mother and 23 from the father HOMOLOGOUS CHROMOSOMES Autosomes o Are
More informationConcurrent Practical Session ACMG Classification
Variant Effect Prediction Training Course 6-8 November 2017 Prague, Czech Republic Concurrent Practical Session ACMG Classification Andreas Laner / Anna Benet-Pagès 1 Content 1. Background... 3 2. Aim
More informationLab Activity 36. Principles of Heredity. Portland Community College BI 233
Lab Activity 36 Principles of Heredity Portland Community College BI 233 Terminology of Chromosomes Homologous chromosomes: A pair, of which you get one from mom, and one from dad. Example: the pair of
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 informationNon-Mendelian inheritance
Non-Mendelian inheritance Focus on Human Disorders Peter K. Rogan, Ph.D. Laboratory of Human Molecular Genetics Children s Mercy Hospital Schools of Medicine & Computer Science and Engineering University
More informationClinical Summaries. CLN1 Disease, infantile onset and others
Clinical Summaries CLN1 Disease, infantile onset and others The gene called CLN1 lies on chromosome 1. CLN1 disease is inherited as an autosomal recessive disorder, which means that both chromosomes carry
More informationDr. Sarah Weckhuysen, MD, PhD. Neurogenetics Group, VIB-Department of Molecular Genetics University of Antwerp, Belgium
Dr. Sarah Weckhuysen, MD, PhD Neurogenetics Group, VIB-Department of Molecular Genetics University of Antwerp, Belgium Sarah Weckhuysen No relevant financial relationships with any commercial interests.
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 informationAdvances in genetic diagnosis of neurological disorders
Acta Neurol Scand 2014: 129 (Suppl. 198): 20 25 DOI: 10.1111/ane.12232 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA Review Article Advances in genetic diagnosis
More informationSialic Acid Storage Diseases
Sialic Acid Storage Diseases Class: BIOL 10001 Instructor: Dr. Vivegananthan Submitted by: Lyndsay Grover Date Submitted: Thursday March 24 th, 2011 Introduction to Sialic Acid Storage Diseases Sialic
More informationMEDICAL GENOMICS LABORATORY. Next-Gen Sequencing and Deletion/Duplication Analysis of NF1 Only (NF1-NG)
Next-Gen Sequencing and Deletion/Duplication Analysis of NF1 Only (NF1-NG) Ordering Information Acceptable specimen types: Fresh blood sample (3-6 ml EDTA; no time limitations associated with receipt)
More informationGaucher disease 3/22/2009. Mendelian pedigree patterns. Autosomal-dominant inheritance
Mendelian pedigree patterns Autosomal-dominant inheritance Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive Y-linked Examples of AD inheritance Autosomal-recessive inheritance
More informationDeciphering Developmental Disorders (DDD) DDG2P
Deciphering Developmental Disorders (DDD) DDG2P David FitzPatrick MRC Human Genetics Unit, University of Edinburgh Deciphering Developmental Disorders objectives research understand genetics of DD translation
More informationA guide to understanding variant classification
White paper A guide to understanding variant classification In a diagnostic setting, variant classification forms the basis for clinical judgment, making proper classification of variants critical to your
More informationSEX-LINKED INHERITANCE. Dr Rasime Kalkan
SEX-LINKED INHERITANCE Dr Rasime Kalkan Human Karyotype Picture of Human Chromosomes 22 Autosomes and 2 Sex Chromosomes Autosomal vs. Sex-Linked Traits can be either: Autosomal: traits (genes) are located
More informationGENETICS AND TREATMENT OF DYSTONIA
GENETICS AND TREATMENT OF DYSTONIA Oksana Suchowersky, M.D., FRCPC, FCCMG Professor of Medicine, Medical Genetics, and Psychiatry Toupin Research Chair in Neurology DYSTONIA Definition: abnormal sustained
More informationLab Activity Report: Mendelian Genetics - Genetic Disorders
Name Date Period Lab Activity Report: Mendelian Genetics - Genetic Disorders Background: Sometimes genetic disorders are caused by mutations to normal genes. When the mutation has been in the population
More informationDistal renal tubular acidosis: genetic and clinical spectrum
Distal renal tubular acidosis: genetic and clinical spectrum Sabrina Giglio Medical Genetics Unit, Meyer Children s University Hospital, University of Florence sabrina.giglio@meyer.it sabrinarita.giglio@unifi.it
More informationMEDICAL GENOMICS LABORATORY. Non-NF1 RASopathy panel by Next-Gen Sequencing and Deletion/Duplication Analysis of SPRED1 (NNP-NG)
Non-NF1 RASopathy panel by Next-Gen Sequencing and Deletion/Duplication Analysis of SPRED1 (NNP-NG) Ordering Information Acceptable specimen types: Blood (3-6ml EDTA; no time limitations associated with
More informationBIOL2005 WORKSHEET 2008
BIOL2005 WORKSHEET 2008 Answer all 6 questions in the space provided using additional sheets where necessary. Hand your completed answers in to the Biology office by 3 p.m. Friday 8th February. 1. Your
More informationTHE ROLE OF CFTR MUTATIONS IN CAUSING CYSTIC FIBROSIS (CF)
THE ROLE OF CFTR MUTATIONS IN CAUSING CYSTIC FIBROSIS (CF) Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210. Vertex and the Vertex triangle logo are registered trademarks for Vertex
More informationGenome Summary. Sequencing Coverage: Variation Counts: Known Phenotype Summary: 131 disease or trait variations are found in this genome
Report Date: August 2, 215 Software Annotation Version: 8 Genome Summary Name: Greg Mendel Genome ID: genome_greg_mendel_dad Sequencing Provider: 23andMe Sequencing Type: Genotyping SNP Array Sequencing
More informationCANCER GENETICS PROVIDER SURVEY
Dear Participant, Previously you agreed to participate in an evaluation of an education program we developed for primary care providers on the topic of cancer genetics. This is an IRB-approved, CDCfunded
More informationMultiple Copy Number Variations in a Patient with Developmental Delay ASCLS- March 31, 2016
Multiple Copy Number Variations in a Patient with Developmental Delay ASCLS- March 31, 2016 Marwan Tayeh, PhD, FACMG Director, MMGL Molecular Genetics Assistant Professor of Pediatrics Department of Pediatrics
More informationChapter 4 PEDIGREE ANALYSIS IN HUMAN GENETICS
Chapter 4 PEDIGREE ANALYSIS IN HUMAN GENETICS Chapter Summary In order to study the transmission of human genetic traits to the next generation, a different method of operation had to be adopted. Instead
More informationICD-9 to ICD-10 Conversion of Epilepsy
ICD-9-CM 345.00 Generalized nonconvulsive epilepsy, without mention of ICD-10-CM G40.A01 Absence epileptic syndrome, not intractable, with status G40.A09 Absence epileptic syndrome, not intractable, without
More informationHuman inherited diseases
Human inherited diseases A genetic disorder that is caused by abnormality in an individual's DNA. Abnormalities can range from small mutation in a single gene to the addition or subtraction of a whole
More informationBIOCHEMICAL AND MOLECULAR HETEROGENEITY IN CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY
BIOCHEMICAL AND MOLECULAR HETEROGENEITY IN CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY Carmen Sousa, Helena Fonseca, Hugo Rocha, Ana Marcão, Laura Vilarinho, Luísa Diogo, Sílvia Sequeira, Cristina Costa,
More informationThalassemias. Emanuela Veras, M.D. 01/08/2006
Thalassemias Emanuela Veras, M.D. 01/08/2006 Structure and Function of normal Hemoglobin molecules: 2/3 1/3 β: increases from 6 th week of fetal life to 12 months of age At birth: HbF: 75-90% HbA: 10-25%
More informationTHIAMINE TRANSPORTER TYPE 2 DEFICIENCY
THIAMINE TRANSPORTER TYPE 2 DEFICIENCY WHAT IS THE THIAMINE TRANSPORTER TYPE 2 DEFICIENCY (hthtr2)? The thiamine transporter type 2 deficiency (hthtr2) is a inborn error of thiamine metabolism caused by
More informationCLINICAL SIGNS SUGGESTIVE OF A NEUROMETABOLIC DISEASE. Bwee Tien Poll-The Amsterdam UMC The Netherlands
CLINICAL SIGNS SUGGESTIVE OF A NEUROMETABOLIC DISEASE Bwee Tien Poll-The Amsterdam UMC The Netherlands FRAMEWORK OF PRINCIPALS 1. Problem-oriented clinical approach 2. Biomarkers in plasma, urine, CSF
More informationAn approach to movement disorders. Kailash Bhatia, DM, FRCP Professor of Clinical Neurology Institute of Neurology Queen Square, London
An approach to movement disorders Kailash Bhatia, DM, FRCP Professor of Clinical Neurology Institute of Neurology Queen Square, London Neurology Diagnosis Two main questions: What parts of the nervous
More informationNGS in neurodegenerative disorders - our experience
Neurology Clinic, Clinical Center of Serbia Faculty of Medicine, University of Belgrade Belgrade, Serbia NGS in neurodegenerative disorders - our experience Marija Branković, MSc Belgrade, 2018 Next Generation
More informationHyperammonemia in Pediatric Clinics: A review of ornithine transcarbamylase deficiency (OTCD) based on our case studies
JMA Medical Awards Hyperammonemia in Pediatric Clinics: A review of ornithine transcarbamylase deficiency (OTCD) based on our case studies JMAJ 47(4): 160 165, 2004 Ichiro MATSUDA Professor Emeritus, Kumamoto
More informationPedigree Construction Notes
Name Date Pedigree Construction Notes GO TO à Mendelian Inheritance (http://www.uic.edu/classes/bms/bms655/lesson3.html) When human geneticists first began to publish family studies, they used a variety
More informationA Comprehensive Study of TP53 Mutations in Chronic Lymphocytic Leukemia: Analysis of 1,287 Diagnostic CLL Samples
A Comprehensive Study of TP53 Mutations in Chronic Lymphocytic Leukemia: Analysis of 1,287 Diagnostic CLL Samples Sona Pekova, MD., PhD. Chambon Ltd., Laboratory for molecular diagnostics, Prague, Czech
More informationCHAPTER 10 BLOOD GROUPS: ABO AND Rh
CHAPTER 10 BLOOD GROUPS: ABO AND Rh The success of human blood transfusions requires compatibility for the two major blood group antigen systems, namely ABO and Rh. The ABO system is defined by two red
More informationProposal form for the evaluation of a genetic test for NHS Service Gene Dossier/Additional Provider
Proposal form for the evaluation of a genetic test for NHS Service Gene Dossier/Additional Provider TEST DISORDER/CONDITION POPULATION TRIAD Submitting laboratory: Exeter RGC Approved: Sept 2013 1. Disorder/condition
More informationHuman Molecular Genetics Prof. S. Ganesh Department of Biological Sciences and Bioengineering Indian Institute of Technology, Kanpur
Human Molecular Genetics Prof. S. Ganesh Department of Biological Sciences and Bioengineering Indian Institute of Technology, Kanpur Module - 02 Lecture - 06 Let us test your understanding of Pedigree
More informationA modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome
DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY ORIGINAL ARTICLE A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome YASUSHI ITO HIROKAZU OGUNI SUSUMU ITO MIYAKO
More informationD-glucose, the essential fuel for brain metabolism,
ORIGINAL ARTICLE Glut1 Deficiency Syndrome and Erythrocyte Glucose Uptake Assay Hong Yang, MD, Dong Wang, MD, Kristin Engelstad, MS, Leslie Bagay, MD, Ying Wei, PhD, Michael Rotstein, MD, Vimla Aggarwal,
More informationHow many disease-causing variants in a normal person? Matthew Hurles
How many disease-causing variants in a normal person? Matthew Hurles Summary What is in a genome? What is normal? Depends on age What is a disease-causing variant? Different classes of variation Final
More informationChapter 16 Mutations. Practice Questions:
Biology 234 J. G. Doheny Chapter 16 Mutations Practice Questions: Answer the following questions with one or two sentences. 1. List the name of one test that can be used to identify mutagens. 2. What is
More informationCharacteristic phasic evolution of convulsive seizure in PCDH19-related epilepsy
Characteristic phasic evolution of convulsive seizure in PCDH19-related epilepsy Hiroko Ikeda 1, Katsumi Imai 1, Hitoshi Ikeda 1, Hideo Shigematsu 1, Yukitoshi Takahashi 1, Yushi Inoue 1, Norimichi Higurashi
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 informationChildhood epilepsy: the biochemical epilepsies. Dr Colin D Ferrie Consultant Paediatric Neurologist Leeds General Infirmary
Childhood epilepsy: the biochemical epilepsies Dr Colin D Ferrie Consultant Paediatric Neurologist Leeds General Infirmary Definitions Epileptic Seizure Manifestation(s) of epileptic (excessive and/or
More informationHuman Blood Groups. ABO Blood Grouping 5/1/12. Dr Badri Paudel Landsteiner s Rule
Human Blood Groups ABO Blood Grouping Dr Badri Paudel www.badripaudel.com RBC membranes have glycoprotein an:gens on their external surfaces These an:gens are: Unique to the individual Recognized as foreign
More informationDr.Abdolreza Afrasiabi
Dr.Abdolreza Afrasiabi Thalassemia & Heamophilia Genetic Reaserch Center Shiraz Medical University Hemoglobin tetramer Hemoglobin Structure % A 1 α 2 β 2 94-97% A 2 α 2 δ 2 2.5% A 1C α 2 (β-n-glucose)
More informationFamilial dystonia with cerebral calcification
Familial dystonia with cerebral calcification case report and genetic update M. Signaevski, A.K. Wszolek, A.J. Stoessel, R. Rademakers, and I.R. Mackenzie Vancouver General Hospital, BC, Canada Mayo Clinic
More informationReport on GLUT1 Deficiency Syndrome Conference
Report on GLUT1 Deficiency Syndrome Conference Chicago, US, July 24th 2009 By W.G. Leen, MD GLUT1 deficiency: from the beginning to now and beyond Dr. D.C. de Vivo (Professor of Pediatrics, Colombia University,
More informationSETPEG GENETIC TESTING GUIDELINES Version 1.0, 5 th October 2017
SETPEG GENETIC TESTING GUIDELINES Version 1.0, 5 th October 2017 1. The Epilepsy Genetic Diagnostic & Counselling Service at King s Health Partners Professor Deb Pal PhD MRCP (Consultant) deb.pal@nhs.net
More informationGenetic Disorders. PART ONE: Detecting Genetic Disorders. Amniocentesis Chorionic villus sampling Karyotype Triple Screen Blood Test
Genetic Disorders PART ONE: Detecting Genetic Disorders Amniocentesis Chorionic villus sampling Karyotype Triple Screen Blood Test Amniocentesis A technique for determining genetic abnormalities in a fetus
More informationGenome Summary. Sequencing Coverage: Variation Counts: Known Phenotype Summary: 152 disease or trait variations are found in this genome
Report Date: August 19, 2015 Software Annotation Version: 8 Genome Summary Name: EUR NA12877 Father Genome ID: NA12877-200-37-ASM Sequencing Provider: Complete Genomics Sequencing Type: Whole Genome Sequencing
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 HEMOCHROMATOSIS, TYPE 4; HFE4 OMIM number for disease #606069 Disease alternative
More informationWhat we know about Li-Fraumeni syndrome
What we know about Li-Fraumeni syndrome Dr Helen Hanson Consultant in Cancer Genetics St Georges Hospital, South-West Thames Regional Genetics Service History of LFS 1969 Li and Fraumeni describe four
More informationSotos syndrome. Nazneen Rahman Institute of Cancer Research
Sotos syndrome Nazneen Rahman Institute of Cancer Research Sotos syndrome- background Sporadic condition Distinctive facial appearance Overgrowth (tall with big heads) Learning difficulties Other variably
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 Parkinson disease 8, automsomal dominant OMIM number for disease 607060 Disease
More informationHuman Genetic Diseases (Ch. 15)
Human Genetic Diseases (Ch. 15) 1 2 2006-2007 3 4 5 6 Genetic counseling Pedigrees can help us understand the past & predict the future Thousands of genetic disorders are inherited as simple recessive
More informationEpilepsy Syndromes: Where does Dravet Syndrome fit in?
Epilepsy Syndromes: Where does Dravet Syndrome fit in? Scott Demarest MD Assistant Professor, Departments of Pediatrics and Neurology University of Colorado School of Medicine Children's Hospital Colorado
More informationNGS panels in clinical diagnostics: Utrecht experience. Van Gijn ME PhD Genome Diagnostics UMCUtrecht
NGS panels in clinical diagnostics: Utrecht experience Van Gijn ME PhD Genome Diagnostics UMCUtrecht 93 Gene panels UMC Utrecht Cardiovascular disease (CAR) (5 panels) Epilepsy (EPI) (11 panels) Hereditary
More informationPondering Epilepsy Classification (actually a few thoughts on the impact of genetic analyses of the epilepsies) Genetics of Epilepsies
Pondering Epilepsy Classification (actually a few thoughts on the impact of genetic analyses of the epilepsies) Dan Lowenstein UCSF Department of Neurology and the UCSF Epilepsy Center To Cover: 1. Update
More informationChinese cases of early infantile epileptic encephalopathy: a novel mutation in the PCDH19 gene was proved in a mosaic male- case report
Tan et al. BMC Medical Genetics (2018) 19:92 https://doi.org/10.1186/s12881-018-0621-x CASE REPORT Open Access Chinese cases of early infantile epileptic encephalopathy: a novel mutation in the PCDH19
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 informationGenetics After Mendel
Genetics After Mendel Genetics After Mendel Single factor inheritance Mendel found traits as dominant or recessive Some instances where the former rule does not apply: Incomplete Dominance Co-dominance
More informationMetabolic Liver Disease
Metabolic Liver Disease Peter Eichenseer, MD No relationships to disclose. Outline Overview Alpha-1 antitrypsin deficiency Wilson s disease Hereditary hemochromatosis Pathophysiology Clinical features
More informationClassification of Seizures. Generalized Epilepsies. Classification of Seizures. Classification of Seizures. Bassel F. Shneker
Classification of Seizures Generalized Epilepsies Bassel F. Shneker Traditionally divided into grand mal and petit mal seizures ILAE classification of epileptic seizures in 1981 based on clinical observation
More informationMMB (MGPG) Non traditional Inheritance Epigenetics. A.Turco
MMB (MGPG) 2017 Non traditional Inheritance Epigenetics A.Turco NON TRADITIONAL INHERITANCE EXCEPTIONS TO MENDELISM - Genetic linkage (2 loci close to each other) - Complex or Multifactorial Disease (MFD)
More informationJuvenile Huntington Disease
Juenile Huntington Disease THE RAREST HD VARIANT when the disease starts before 20 years of age Ferdinando Squitieri M.D., Ph.D. - Neurologist, Head of the HD Unit, IRCCS Casa Sollieo della Sofferenza
More informationTay Sachs, Cystic Fibrosis, Sickle Cell Anemia and PKU. Tay Sachs Disease (also called Hexosaminidase deficiency)
Tay Sachs, Cystic Fibrosis, Sickle Cell Anemia and PKU Tay Sachs Disease (also called Hexosaminidase deficiency) Introduction 1. Tay Sachs is a rare condition named after 2 physicians, Tay and Sachs, who
More informationFigure 1: Transmission of Wing Shape & Body Color Alleles: F0 Mating. Figure 1.1: Transmission of Wing Shape & Body Color Alleles: Expected F1 Outcome
I. Chromosomal Theory of Inheritance As early cytologists worked out the mechanism of cell division in the late 1800 s, they began to notice similarities in the behavior of BOTH chromosomes & Mendel s
More informationMovement disorders: The border between the psychogenic and the neurological. Chiclana G, Ojeda J, Mata M, Chiclana C, Gutiérrez G, Miralles A,.
Movement disorders: The border between the psychogenic and the neurological Chiclana G, Ojeda J, Mata M, Chiclana C, Gutiérrez G, Miralles A,. 1. Introduction 2. Cases Report 3. Conclusions 1. Introduction
More informationRiunione Regionale SIN Campania
Riunione Regionale SIN Campania Dott.ssa Maria Lieto Dipartimento di Neuroscienze, Università Federico II Napoli Salerno, 14 dicembre 2018 HEREDITARY ATAXIAS SCAs (35 genes) ARCAs (94 genes) Diagnosis?
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 informationHuman Genetic Diseases. AP Biology
Human Genetic Diseases 1 2 2006-2007 3 4 5 6 Pedigree analysis Pedigree analysis reveals Mendelian patterns in human inheritance data mapped on a family tree = male = female = male w/ trait = female w/
More informationGenetics and Genomics in Endocrinology
Genetics and Genomics in Endocrinology Dr. Peter Igaz MD MSc PhD 2 nd Department of Medicine Faculty of Medicine Semmelweis University Genetics-based endocrine diseases I. Monogenic diseases: Multiple
More informationMovement disorders in childhood: assessment and diagnosis. Lucinda Carr
Movement disorders in childhood: assessment and diagnosis Lucinda Carr Movement disorders in childhood: Assessment Classification Causes Diagnosis Presentation of movement disorders in childhood: Concerns
More informationDr. Ayman Mohsen Mashi, MBBS Consultant Hematology & Blood Transfusion Department Head, Laboratory & Blood Bank King Fahad Central Hospital, Gazan,
Dr. Ayman Mohsen Mashi, MBBS Consultant Hematology & Blood Transfusion Department Head, Laboratory & Blood Bank King Fahad Central Hospital, Gazan, KSA amashi@moh.gov.sa 24/02/2018 β-thalassemia syndromes
More informationWelcome to the Genetic Code: An Overview of Basic Genetics. October 24, :00pm 3:00pm
Welcome to the Genetic Code: An Overview of Basic Genetics October 24, 2016 12:00pm 3:00pm Course Schedule 12:00 pm 2:00 pm Principles of Mendelian Genetics Introduction to Genetics of Complex Disease
More informationThe laws of Heredity. Allele: is the copy (or a version) of the gene that control the same characteristics.
The laws of Heredity 1. Definition: Heredity: The passing of traits from parents to their offspring by means of the genes from the parents. Gene: Part or portion of a chromosome that carries genetic information
More informationCorporate Medical Policy
Corporate Medical Policy File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_testing_for_rett_syndrome 7/2012 3/2017 3/2018 5/2017 Description of Procedure or Service Rett syndrome
More informationSection Chapter 14. Go to Section:
Section 12-3 Chapter 14 Go to Section: Content Objectives Write these Down! I will be able to identify: The origin of genetic differences among organisms. The possible kinds of different mutations. The
More informationThe Complexity of Simple Genetics
The Complexity of Simple Genetics? The ciliopathies: a journey into variable penetrance and expressivity Bardet-Biedl Syndrome Allelism at a single locus is insufficient to explain phenotypic variability
More informationEvaluation and management of drug-resistant epilepsy
Evaluation and management of drug-resistant epilepsy Fateme Jahanshahifar Supervised by: Professor Najafi INTRODUCTION 20 to 40 % of patients with epilepsy are likely to have refractory epilepsy. a substantive
More informationGenotype-Phenotype in Egyptian Patients with Nephropathic Cystinosis. (December 2012 report)
Genotype-Phenotype in Egyptian Patients with Nephropathic Cystinosis (December 2012 report) This is the first study of the genotype of Nephropathic Cystinosis (NC) patients in Egypt and the region of North
More information