Screen Positive Follow-up In The Clinic
|
|
- Gregory Taylor
- 5 years ago
- Views:
Transcription
1 Screen Positive Follow-up In The Clinic NBS Molecular Training Workshop April 2016 Sherly Pardo-Reoyo, M.D. Medical Geneticist Assistant Professor Dept. Biochemistry & Pediatrics UPR-School of Medicine Clinical Director MSMS and Molecular Laboratories PR-NBS Program
2 Newborn Screening (NBS) Goals Ultimately the goals of newborn screening are to prevent the morbidity and mortality of infants by the early identification of various diseases.
3 U.S. Dept of Health and Human Services. Discretionary Advisory Committee of Heritable Disorders in Newborns and Children.
4 U.S. Dept of Health and Human Services. Discretionary Advisory Committee of Heritable Disorders in Newborns and Children.
5 Success stories
6
7 Newborn Screening (NBS) TIMELINESS -Sample to be collected within hours of life. -Sample to be delivered to the NBS Lab within 24 hours of being collected. -NBS tests to be completed and reported within day 5 of life for timecritical conditions and at least by the 7 day of life for all others.
8 Arizona, Colorado and Wyoming, California, Hawaii, Iowa, Michigan, Minnesota, Montana, Nebraska; Delaware, Maryland, New Jersey, New York; Oklahoma, Puerto Rico, Tennessee, Texas, Virginia, Wisconsin
9 NBS Beyond a dried blood spot.
10 NBS Components www1.newbornscreening.ph Health care systems affect the TIMELINESS for prompt confirmation and management.
11 Biochemical assay limitations Factors that affect a biochemical assay: age of infant at the time of sample collection, feeding status of infant at the time of sample collection, medications, population cut-offs. There is a differential diagnosis or set of disorders associated to a particular biochemical marker identified by NBS tests. Most metabolic disorders are inherited in an autosomal recessive manner. Most patients do not have a null mutation causing 0% enzyme activity thus levels of biochemical makers, age of onset, disease severity is variable. Sometimes mild elevations in biochemical markers are due to maternal conditions or a partial deficiency in carriers who would not develop the disease. SECOND TIER TESTS BIOCHEMICAL MOLECULAR
12 Molecular assay limitations Molecular tests are as good as it is their design: targeted, sequencing, rearrangement analysis. -Allele drop-out (false-negative results) Molecular test results are as good as the available evidence to determine their clinical significance. -Variants of uncertain significance (VUS) -Pseudogenes: NOT all biochemical abnormalities (elevation of disease markers or even proven in vitro enzyme deficiencies) are associated with disease onset. Many physicians and/or health professionals are not aware of these and might use or interpret the NBS or any molecular test results inappropriately.
13 Your screen is positive on a 5 day old infant now what? The clock is ticking Toxic substances and/or secondary deficiencies are building up and causing damage some irreversible. Journal Sentinel
14 Diagnostic Guidelines For many genetic conditions, MOLECULAR TESTS are enough to establish the diagnosis without the need for active disease manifestations or further tests. A few examples are: -Marfan Syndrome -Neurofibromatosis Type 1 -Duchenne/Becker Muscular Dystrophy -Cystic Fibrosis For many others it is still recommended to conduct MOLECULAR TESTS to guide management and for prognosis.
15 Do not forget there are various mechanisms that result in mutations/variations.
16 Examples of tests and mutation types in NBS screened disorders.
17 Study Case #1 CASES FOR DISCUSSION
18 Cystic Fibrosis Study Case #1 Baby boy #2 is a 35 week old born by cesarean section due to failure to progress after 14 hours in labor. The infant was born lethargic with significant aspiration of meconium. He was stabilized and sent to the neonatal intensive care unit with ventilatory support and placed on total parenteral nutrition. The newborn screening sample was obtained at 40 hours of age and sent to the NBS laboratory within 24 hours of collection. On day of life 4 the infant is still lethargic and a sepsis work up was started. Meconium was passed on day of life 1. On the second day of life a Genetics consult was placed since the infant has a heart defect and some unusual features. On day of life 5 the NBS Lab calls in since the CF screening test was positive. They report that the infant s IRT level was elevated. They perform targeted molecular tests for certain mutations and they found one, F508del. The family history reveals that the parents are first cousins. They just arrived from Asia and they do not have medical insurance.
19 What to do next? Option 1: You decide to send a second sample to the NBS laboratory for confirmation. Option 2: You decide to refer to a CF Center for sweat testing once the infant is discharged. Option 3: You decide to send for full sequencing of the gene prior to sweat testing.. All assays including NBS tests have their limitations. You should know them before making your follow-up and/or re-testing algorithm.
20 CF Clinical features Obstruction of tubular structures by viscous secretions. Respiratory system Gastrointestinal system en.wikipedia.org
21 CF Professional Guidelines Sweat test: $ Gene sequencing: >$1000
22 CF Professional Guidelines cont.
23 CFTR mutation/variation databases: CFTR1 and CFTR2
24
25 Clinical Effects of Various CFTR Mutation Combinations Table 4. Genotype-Phenotype Correlations: Cystic fibrosis CFTR Genotype 1 First Allele Second Allele (or Homozygous) Range of Phenotypes 2 Classic (e.g., ΔF508) Classic Classic >> non-classic Mild (e.g., A455E) Classic or mild Non-classic > classic R117H/5T Classic or mild Non-classic > classic R117H/7T 5T/TG13 or TG12 Classic or mild Classic or mild Asymptomatic female or CAVD > non-classic CAVD or non-classic CF >> asymptomatic carrier 5T/TG11 Classic or mild Asymptomatic > CAVD 7T or 9T Classic or mild Asymptomatic 7T or 9T 7T or 9T Asymptomatic
26 WOULD THE MOLECULAR TEST AFFECT THE MANAGEMENT OF A CF PATIENT?
27 Precision medicine/ Genotype-based management: CF Kalydeco (ivacaftor), 150 mg po bid, Is a FDA approved prescription medicine used for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have one of the following mutations in their CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R. KALYDECO was granted Breakthrough Therapy designation by the U.S. FDA in late 2012 and FDA approval in January 21, Ivacaftor facilitates increased Cl - transport by potentiating the channel-open probability (Class III mutations). Kalydeco costs ~$290,000 per year per patient. G551D-CFTR protein defect without KALYDECO G551D-CFTR protein defect with KALYDECO
28 Adults and children 12 years and older should take 2 tablets by mouth every 12 hours. The wholesale acquisition cost per dose (2 tablets) is $354.80, equating to an annual cost of $259,000 per year per patient. Jennifer L. Cruz, PharmD, BCPS, and Katherine Summers, PharmD candidate Published Online: Friday, November 20, 2015//
29 DO WE KNOW ALL ABOUT CFTR MUTATIONS?
30 ClinVar Database: CFTR CFTR mutations have been well studied for years. Do we already know everything about them?
31 What to do next? Option 1: You decide to send a second sample to the NBS laboratory for confirmation. Option 2: You decide to refer to a CF Center for sweat testing once the infant is discharged. Option 3: The infant might stay in the NICU for several weeks. Therefore you decide to send for full sequencing of the gene prior to sweat testing.. All assays including NBS tests have their limitations. You should know them before making your follow-up and/or re-testing algorithm.
32 Study Case #2 CASES FOR DISCUSSION
33 Hyperphenylalaninemia Study Case 2 Baby boy #1 is a 35 week old born by cesarean section due to failure to progress after 14 hours in labor. The infant was born lethargic with significant aspiration of meconium. He was stabilized and sent to the neonatal intensive care unit with respiratory support and placed on intravenous fluids. The newborn screening sample was obtained at 28 hours of age and sent to the NBS laboratory within 24 hours of collection. On day 3 of life the infant was still lethargic requiring ventilatory support and his nutrition was changed to total parenteral nutrition and intralipids. On day of life 5 the NBS Lab calls in since the PKU screening test was positive. They report that the infants level of phenylalanine was 5 mg/dl and the population cut off is 2 mg/dl. They perform targeted molecular tests for certain mutations and they found one, R408W. The family history reveals that the parents are first cousins. They just arrived from Ireland and they do not have medical insurance.
34 What to do next? Option 1: You don t do anything because the levels were mildly elevated and since there was only one mutation identified he is most likely a carrier. Option 2: You ask for a second sample to repeat the NBS test. Option 3: You start a PKU diet/treatment ASAP.
35 PKU Professional Guidelines
36 PKU Professional Guidelines cont.
37 Phenylalanine metabolism Thyroxine Melanins Tyrosine Hydroxylase phedup.co.uk/images/untreated-pku.jpg
38
39 WOULD THE MOLECULAR TEST AFFECT THE MANAGEMENT OF A PATIENT WITH HYPERPHENYLALANINEMIA?
40 Precision medicine/ Genotype-based management: Hyperphenylalaninemia
41 Diagnostic work up. Plasma amino acids (PAA): >$230 Urine organic acids (UOA): >$230 Gene Sequencing: >$1000 Pterins: ~$700
42
43
44 DO WE KNOW ALL ABOUT PAH GENE MUTATIONS?
45 ClinVar Database: PAH
46 What to do next? Option 1: You don t do anything because the levels were mildly elevated and since there was only one mutation identified he is most likely a carrier. Option 2: You ask for a second sample to repeat the NBS test. Option 3: You start a PKU formula/treatment ASAP.
47 CAN WE START THE CORRESPONDING BREAKTHROUGH MANAGEMENT AND THEN DISCONTINUE IT IF NOT NEEDED?
48 As you can see, at current pricing, the cost of Naglazyme will pass $1 million as patients hit their teen years, and reach $1.3 million as they approach their 40s. Of course, it s not certain that this will happen; one could imagine that the price may need to drop over the coming decades. But this shows how very expensive these drugs are.
49 WHAT IS THE DIFFERENCE BETWEEN BIOCHEMICAL OR MOLECULAR GENETIC TEST REPORTS AND OTHER CLINICAL TEST REPORTS?
50 Consensus guidelines for sequencing reports.
51 Consensus guidelines for sequencing reports cont. Use the term variant with the following modifiers: (i) pathogenic (ii) likely pathogenic (iii) uncertain significance (VUS) (iv) likely benign (v) benign
52 Consensus guidelines for sequencing reports cont. A. Use of standardized terminology and established databases for reporting sequence variants 1. Nomenclature. A uniform nomenclature is recommended to ensure the unambiguous designation of a variant and enable effective sharing and downstream use of genomic information. A standard gene variant nomenclature ( is maintained and versioned by the Human Genome Variation Society (HGVS). 2. Reference sequence A standard reference sequence for each gene should be used and derived from the NCBI refseq database. The origin of the transcript used should be specified, e.g., the most common human transcript, largest known transcript, or tissue-specific alternatively spliced transcript. 3. Databases Sequence databases. Disease-specific databases. Population databases. However, disease and gene-specific databases often contain variants that are incorrectly classified. Specify: -The frequency with which the database is curated and the latest update; -Evidence for variant classification (it is recommended to check the original cited reference); -Number of times the variant has been reported; -Populations in which a variant has been reported.
53
54 Human mutation/variation registries.
55 How to determine the clinical significance of VUS?
56 THE MOLECULAR ASSAY IS AS GOOD AS EACH OF ITS COMPONENTS: THE DESIGN, VALIDATION, ANALYSIS, BIOINFORMATICS.
57 PERSONAL EXAMPLES TO EXERT CAUTION WITH THE INTERPRETATION OF MOLECULAR RESULTS. Design and analysis: do not believe the first reference you find. OMIM c.695a>g... It is not on exon 5 of PAH, and does not result in R158Q
58 Amino acid (R) 158 is cdna positions c.695a>g is actually Q232R
59 Design and analysis: PAH discrepancies in gdna and cdna NCBI reference sequences. c.1155c>g; Exon 11
60 OTHER EXAMPLES TO EXERT CAUTION WHEN INTERPRETING MOLECULAR TESTS RESULTS.
61 ClinVar: Examples of how rapidly the data in the registry changes. BRCA2 gene: ~89,000 nucleotides 3418 amino acids Reported as pathogenic mutations: 1256 total 419 multiple submitters (as of May ) PALB2 gene: ~45,000 nucleotides 1186 amino acids Reported as pathogenic mutations: 12 (as of Dic ) 138 (as of May ), 37 by multiple submitters
62 Discrepancy among protein predictive models.
63 Optional supplementary reports
64 Discrepancy in the reference sequences used by laboratories and mutation registries.
65 Things to remember -Allele drop out can occur. -Bioinformatics can add bias. -Clinical mutations databases are not complete or the classifications are not always accurate. -There can be discrepancies on reference sequences and protein prediction models. -Most physicians who will receive the data/results are not molecularly savvy/competent. -NOT ALL molecular methods identify all possible genomic defects. A number of genomic alterations are due to rearrangements often missed on various molecular methods used regularly for identifying missense mutations. [Sanger Sequencing: >$1000; Del/Duplication analysis: >$700]
66 Summary. Molecular tests can be useful for screening, diagnosis, and prognosis. Remember that molecular tests have limitations. [Physicians must follow up the patients, if some manifestations develop then consider further molecular testing including del/dup analysis]. Further education of healthcare professionals and/or Genetic Counseling regarding the need, utility and results interpretation for various molecular tests is necessary. Mutation/variant registries as well as natural history studies are necessary.
Medical Policy An independent licensee of the Blue Cross Blue Shield Association
Cystic Fibrosis Transmembrane Page 1 of 11 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Prime Therapeutics
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
Cystic Fibrosis Transmembrane Page 1 of 13 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Prime Therapeutics
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 informationPediatrics Grand Rounds 13 November University of Texas Health Science Center at San Antonio. Learning Objectives
Nationwide Newborn Screening for Cystic Fibrosis: Finally Creating an Opportunity for All Patients to Have Better Outcomes Philip M Farrell, MD, PhD* University of Wisconsin-Madison *No disclosures other
More informationPA Update: Oral Cystic Fibrosis Modulators
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationGene Sequencing in Newborn Screening: Covering the Bases of Education and Follow-Up. Amy Gaviglio, MS, CGC February 17, 2017
Gene Sequencing in Newborn Screening: Covering the Bases of Education and Follow-Up Amy Gaviglio, MS, CGC February 17, 2017 Outline Education Personnel Case Examples Considerations EDUCATION: OUR BASELINE
More informationTesting for Genetic Disorders that Cause Brain Damage
STO-132 Testing for Genetic Disorders that Cause Brain Damage Part 1: Newborn Screening Tests Matt is watching his twins, Anna and Cody, in the newborn nursery. The nurse pokes the babies heels, collects
More informationLong-term Follow-up for Cystic Fibrosis: A Collaboration with the Cystic Fibrosis Foundation
Long-term Follow-up for Cystic Fibrosis: A Collaboration with the Cystic Fibrosis Foundation Beth Vogel, MS, CGC NYS Newborn Screening Program Wadsworth Center Outline Introduction Matching Long-term follow-up
More informationKalydeco. Kalydeco (ivacaftor) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.45.03 Subject: Kalydeco Page: 1 of 6 Last Review Date: November 30, 2018 Kalydeco Description Kalydeco
More informationPharmacogenomics in Rare Diseases: Development Strategy for Ivacaftor as a Therapy for Cystic Fibrosis
Pharmacogenomics in Rare Diseases: Development Strategy for Ivacaftor as a Therapy for Cystic Fibrosis Federico Goodsaid Vice President Strategic Regulatory Intelligence Vertex Pharmaceuticals Is there
More informationIVACAFTOR THE ISRAELI EXPERIENCE ADI DAGAN MD THE ISRAELI CF CENTER SHEBA MEDICAL CENTER, TEL-HASHOMER
IVACAFTOR THE ISRAELI EXPERIENCE ADI DAGAN MD THE ISRAELI CF CENTER SHEBA MEDICAL CENTER, TEL-HASHOMER February 21, 2014 U.S. Food and Drug Administration Approves KALYDECO (ivacaftor) for Use in Eight
More informationBriefing Document. FDA Pulmonary - Allergy Drugs Advisory Committee
FDA Advisory Committee Briefing Materials Page 1 of 157 Briefing Document FDA Pulmonary - Allergy Drugs Advisory Committee Ivacaftor for the Treatment of Cystic Fibrosis in Patients Age 6 Years and Older
More informationWhat is the inheritance pattern (e.g., autosomal, sex-linked, dominant, recessive, etc.)?
Module I: Introduction to the disease Give a brief introduction to the disease, considering the following: the symptoms that define the syndrome, the range of phenotypes exhibited by individuals with the
More informationACEP National H1N1 Preparedness Survey Results
1) On a scale from 1 to 10 (10 being totally prepared and 1 being totally unprepared), do you think your hospital is prepared to manage a surge of H1N1 flu patients this fall and winter? (totally prepared)
More informationImportance of Clinical Information for Optimal Genetic Test Selection and Interpretation
Importance of Clinical Information for Optimal Genetic Test Selection and Interpretation Chris Miller, MS, LCGC ARUP Laboratories Learning Objectives Understand the relevance of clinical information for
More informationCYSTIC FIBROSIS. The condition:
CYSTIC FIBROSIS Both antenatal and neonatal screening for CF have been considered. Antenatal screening aims to identify fetuses affected by CF so that parents can be offered an informed choice as to whether
More informationPediatrics Grand Rounds 18 Sept University of Texas Health Science Center. + Disclosure. + Learning Objectives.
Disclosure Dr Donna Willey Courand receives research support from Cystic Fibrosis Therapeutics The Cystic Fibrosis Foundation Children with Special Health Care Needs Cystic Fibrosis 05: Improving Survival
More informationOral Cystic Fibrosis Modulators
Oral Cystic Fibrosis Modulators Goals: To ensure appropriate drug use and limit to patient populations in which they have demonstrated to be effective and safe. To monitor for clinical response for appropriate
More informationCirrhosis and Liver Cancer Mortality in the United States : An Observational Study Supplementary Material
Cirrhosis and Liver Cancer Mortality in the United States 1999-2016: An Observational Study Supplementary Material Elliot B. Tapper MD (1,2) and Neehar D Parikh MD MS (1,2) 1. Division of Gastroenterology
More informationPrevalence of Self-Reported Obesity Among U.S. Adults by State and Territory. Definitions Obesity: Body Mass Index (BMI) of 30 or higher.
Prevalence of Self-Reported Obesity Among U.S. Adults by State and Territory Definitions Obesity: Body Mass Index (BMI) of 30 or higher. Body Mass Index (BMI): A measure of an adult s weight in relation
More informationAn Effective Model to Communicate Complex Genetic Information to Families and Health Care Providers
An Effective Model to Communicate Complex Genetic Information to Families and Health Care Providers Theresa Steckel, RN, BSN Newborn Screening Quality Assurance and Education Coordinator Oklahoma State
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 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 informationHA Convention 2016 Master course How to Handle Abnormal Newborn Metabolic Screening Results Causes, Management and Follow up
HA Convention 2016 Master course How to Handle Abnormal Newborn Metabolic Screening Results Causes, Management and Follow up Dr. Josephine Chong Clinical Professional Consultant Centre of Inborn Errors
More informationChapter 1: What is PKU?
Chapter 1: What is PKU? A Parent's Perspective "If our child with PKU had been our first instead of our third, or if we had wanted more children after we had her, we would have done so, even knowing the
More information5. Galactosemia. 5.0 Introduction. 5.3 Laboratory Techniques. 5.4 Initial Screening Results. 5.1 Definitions for Classical Galactosemia
5. Galactosemia 5.0 Introduction Screening for galactosemia began in some screening programs in the 1960 s although most programs developed their programs later. In some programs, there is still debate
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 of Vertex
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 informationPhenylketonuria (PKU) the Biochemical Basis. Biol 405 Molecular Medicine
Phenylketonuria (PKU) the Biochemical Basis Biol 405 Molecular Medicine PKU a history In 1934 Følling identified a clinical condition - imbecillitas phenylpyruvica. Mental retardation associated with this
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 informationA Genetic Approach to the Treatment of Cystic Fibrosis
A Genetic Approach to the Treatment of Cystic Fibrosis Peter Mueller, PhD Chief Scientific Officer and Executive Vice President Global Research and Development Vertex Pharmaceuticals, Incorporated March
More informationPKU PKU. Phenylketonuria TEMPLE. Information for families following Information for families after a positive newborn screening
PKU Phenylketonuria PKU Information for families following newborn a positive screening newborn screening Information for families after a positive newborn screening Information for families after a positive
More informationBenefits and pitfalls of new genetic tests
Benefits and pitfalls of new genetic tests Amanda Krause Division of Human Genetics, NHLS and University of the Witwatersrand Definition of Genetic Testing the analysis of human DNA, RNA, chromosomes,
More informationNewborn Bloodspot Screening Information for parents
Newborn Bloodspot Screening Information for parents You will be offered a bloodspot screening test for your newborn baby for several rare but serious conditions. The sample for this test is usually taken
More information2012 Medicaid and Partnership Chart
2012 Medicaid and Chart or Alabama $525,000.00 $4,800.00 Minimum: 25,000.00 Alaska $525,000.00 Depends on area of state; Minimum: $113,640 $10,000 in Anchorage $1,656 Minimum:$1838.75 Maximum:$2,841 Minimum:
More information"Management and Treatment of Patients with Cystic fibrosis (CF)
"Management and Treatment of Patients with Cystic fibrosis (CF) Dr. Malena Cohen-Cymberknoh Pediatric Pulmonology and CF Center Hadassah Hebrew-University Medical Center Jerusalem, Israel Afula, March
More informationHeartland Genetics and Newborn Screening Collaborative Conference
Heartland Genetics and Newborn Screening Collaborative Conference Laurel K. Willig, MD Assistant Medical Director for the Center for Pediatric Genomic Medicine and Joshua E. Petrikin, MD Director of Neonatal
More informationVariant Classification: ACMG recommendations. Andreas Laner MGZ München
Variant Classification: ACMG recommendations Andreas Laner MGZ München laner@mgz-muenchen.de OVERVIEW Introduction ACMG-AMP Classification System Evaluation of inter-laboratory concordance in variant classification
More informationInformation for health professionals
Changes to the Newborn Bloodspot Screening Policy for Congenital Hypothyroidism (CHT) in Preterm Babies A UK policy change has been agreed that will mean changes to: which preterm babies require second
More informationNewborn Bloodspot Screening Information for parents
Newborn Bloodspot Screening Information for parents You will be offered a bloodspot screening test for your newborn baby for several rare but serious conditions. The sample for this test is usually taken
More informationGeorgina Peacock, MD, MPH
Autism Activities at CDC Act Early Region IX Summit Sacramento, CA June 8, 2009 Georgina Peacock, MD, MPH National Center on Birth Defects and Developmental Disabilities Autism Activities at CDC Surveillance/Monitoring
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 information- Aya Alomoush. - Talal Al-Zabin. - Belal Azab. 1 P a g e
24 - Aya Alomoush - Talal Al-Zabin - Belal Azab 1 P a g e 1) Features of autosomal dominant inheritance: A) Vertical transmission: direct transmission from grandparent to parent to child without skipping
More informationImportance of Clinical Information for Optimal Genetic Test Selection and Interpretation. Chris Miller, MS, LCGC ARUP Laboratories
Importance of Clinical Information for Optimal Genetic Test Selection and Interpretation Chris Miller, MS, LCGC ARUP Laboratories Learning Objectives Explain the relevance of clinical information for genetic
More information2018 HPV Legislative Report Card
2018 HPV Legislative Report Card This report card is a snapshot of each state s documented efforts to enact or introduce HPV vaccine legislation to improve education and awareness, or provide access to
More informationEvaluation of Patients with Diffuse Bronchiectasis
Evaluation of Patients with Diffuse Bronchiectasis Dr. Patricia Eshaghian, MD Assistant Clinical Professor of Medicine Director, UCLA Adult Cystic Fibrosis Affiliate Program UCLA Division of Pulmonary
More informationPiero Rinaldo, Si Houn Hahn, Dietrich Matern. Biochemical Genetics Laboratory Mayo Clinic College of Medicine Rochester, MN
Improved Specificity of Newborn Screening for Congenital Adrenal Hyperplasia (CAH) by Second Tier Steroid Profiling using Tandem Mass Spectrometry (MS/MS) Piero Rinaldo, Si Houn Hahn, Dietrich Matern Biochemical
More informationNational Deaf Center on Postsecondary Outcomes. Data Interpretation Guide for State Reports: FAQ
National Deaf Center on Postsecondary Outcomes Data Interpretation Guide for State Reports: FAQ This document was developed under a grant from the U.S. Department of Education, OSEP #HD326D160001. However,
More informationTIMELINESS IN NEWBORN SCREENING: CONSIDERATIONS FOR CYSTIC FIBROSIS
TIMELINESS IN NEWBORN SCREENING: CONSIDERATIONS FOR CYSTIC FIBROSIS Susanna A. McColley, MD Northwestern University Feinberg School of Medicine Ann & Robert H. Lurie Children s Hospital of Chicago Stanley
More informationPrecision Medicine and Genetic Counseling : Is Yes always the correct answer?
Precision Medicine and Genetic Counseling : Is Yes always the correct answer? Beverly M. Yashar, MS, PhD, CGC Director, Graduate Program in Genetic Counseling Professor, Department of Human Genetics. (yashar@umich.edu)
More informationTitle: Assessing Recommendations Related To Timeliness of Newborn Screening
Title: Assessing Recommendations Related To Timeliness of Newborn Screening Purpose: In January 2014, the Secretary s Discretionary Advisory Committee on Heritable Diseases on Newborns and Children (Committee)
More informationInstant Drug Testing State Law Guide
Instant Drug Testing State Law Guide State Alabama Alaska Arizona POCT / Instant Testing Status Comment outside this voluntary law but not by companies that wish to qualify for the WC discount. FDA-cleared
More informationVariant Classification: ACMG recommendations. Andreas Laner MGZ München
Variant Classification: ACMG recommendations Andreas Laner MGZ München laner@mgz-muenchen.de Overview Introduction ACMG-AMP Classification System Evaluation of inter-laboratory concordance in variant classification
More informationB&T Format. New Measures. Better health care. Better choices. Better health.
1100 13th Street NW, Third Floor Washington, DC 20005 phone 202.955.3500 fax 202.955.3599 www.ncqa.org TO: Interested Organizations FROM: Patrick Dahill, Assistant Vice President, Policy DATE: February
More informationForensic Patients in State Hospitals:
Forensic Patients in State Hospitals: 1999-2016 Vera Hollen, M.A. Senior Director of Research & Consulting Director, Mental Health/Criminal Justice Research Center National Association of State Mental
More informationSequencing in Newborn Screening Introduction and Background
Sequencing in Newborn Screening Introduction and Background Suzanne Cordovado, PhD Newborn Screening and Molecular Biology Branch Division of Laboratory Sciences Centers for Disease Control and Prevention
More informationIntroduction to Evaluating Hereditary Risk. Mollie Hutton, MS, CGC Certified Genetic Counselor Roswell Park Comprehensive Cancer Center
Introduction to Evaluating Hereditary Risk Mollie Hutton, MS, CGC Certified Genetic Counselor Roswell Park Comprehensive Cancer Center Objectives Describe genetic counseling and risk assessment Understand
More informationPurpose. Newborn Screening- UC 260. What is NBS? What isn t NBS? History. History 2
Purpose Newborn Screening- UC 260 Edward B. Goldman, J.D. Health System Attorney University of Michigan November 13, 2003 We will review newborn screening (NBS) history Look at current NBS practices Discuss
More informationUsing Policy, Programs, and Partnerships to Stamp Out Breast and Cervical Cancers
Using Policy, Programs, and Partnerships to Stamp Out Breast and Cervical Cancers National Conference of State Legislatures Annual Meeting J August 2006 Christy Schmidt Senior Director of Policy National
More informationCDC activities with Autism Spectrum Disorders
CDC activities with Autism Spectrum Disorders Georgina Peacock, MD, MPH Centers for Disease Control and Prevention National Center on Birth Defects and Developmental Disabilities The findings and conclusions
More informationObesity Trends:
Obesity Trends: 1985-2014 Compiled by the Centers for Disease Control and Prevention Retrieved from http://www.cdc.gov/obesity/data/prevalencemaps.html Organized into two groupings due to methodological
More informationCystic Fibrosis 8/23/2014 GROWTH DEFICIENCY IN CYSTIC FIBROSIS IS
8/23/214 GROWTH DEFICIENCY IN CYSTIC FIBROSIS IS OBSERVABLE AT BIRTH AND PREDICTIVE OF EARLY PULMONARY FUNCTION by Rebecca Joan Nelson Case Western Reserve University Cleveland, Ohio Thesis Advisor: Rebecca
More informationTEMPLE. Tools Enabling Metabolic Parents LEarning ADAPTED BY THE DIETITIANS GROUP. British Inherited Metabolic Diseases Group
TEMPLE Tools Enabling Metabolic Parents LEarning ADAPTED BY THE DIETITIANS GROUP British Inherited Metabolic Diseases Group BASED ON THE ORIGINAL TEMPLE WRITTEN BY BURGARD AND WENDEL PKU Information for
More informationWhen bad things happen to good genes: mutation vs. selection
When bad things happen to good genes: mutation vs. selection Selection tends to increase the frequencies of alleles with higher marginal fitnesses. Does this mean that genes are perfect? No, mutation can
More informationFAMILY PLANNING DOESN T HAVE TO BE ONE OF THEM
THE ESSENTIAL PANEL There are many unknowns in life. FAMILY PLANNING DOESN T HAVE TO BE ONE OF THEM PLANNING FOR A FAMILY IS A BIG DECISION TAKE STEPS TOWARD A HEALTHY FUTURE WITH NXGEN GENETIC CARRIER
More informationCost-effectiveness of Ivacaftor (Kalydeco ) for the treatment of cystic fibrosis in patients age 6 years and older who have the G551D mutation
Cost-effectiveness of Ivacaftor (Kalydeco ) for the treatment of cystic fibrosis in patients age 6 years and older who have the G551D mutation January 2013 1. A rapid review submission on the drug ivacaftor
More informationSupplementary appendix
Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Moss RB, Flume PA, Elborn JS, et al, on behalf
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 Amyotrophic Lateral Sclerosis 10 (ALS10) and Amyotrophic Lateral Sclerosis 6 (ALS6)
More informationThe Genetics of Breast and Ovarian Cancer Prof. Piri L. Welcsh
The Genetics of Breast Piri L. Welcsh, PhD Research Assistant Professor University of Washington School of Medicine Division of Medical Genetics 1 Genetics of cancer All cancers arise from genetic and
More informationPALB2 c g>c is. VARIANT OF UNCERTAIN SIGNIFICANCE (VUS) CGI s summary of the available evidence is in Appendices A-C.
Consultation sponsor (may not be the patient): First LastName [Patient identity withheld] Date received by CGI: 2 Sept 2017 Variant Fact Checker Report ID: 0000001.5 Date Variant Fact Checker issued: 12
More informationSTATE RANKINGS REPORT NOVEMBER mississippi tobacco data
STATE RANKINGS REPORT NOVEMBER 2017 mississippi tobacco data METHODS information about the data sources the youth risk behavior surveillance system The Youth Risk Behavior Surveillance System (YRBSS)
More informationCh 7 Extending Mendelian Genetics
Ch 7 Extending Mendelian Genetics Studying Human Genetics A pedigree is a chart for tracing genes in a family. Used to determine the chances of offspring having a certain genetic disorder. Karyotype=picture
More informationAutism Activities at CDC: The Public Health Model
Autism Activities at CDC: The Public Health Model Act Early Region II Summit Bronx, NY March 26, 2009 Marshalyn Yeargin-Allsopp, MD Georgina Peacock, MD, MPH National Center on Birth Defects and Developmental
More informationSave Lives and Money. Help State Employees Quit Tobacco
Save Lives and Money Help State Employees Quit Tobacco 2009 Join These 5 Leading States Cover All the Treatments Your State Employees Need To Quit Tobacco 1 2 Follow these leaders and help your state employees
More informationThe Healthy Indiana Plan
The Healthy Indiana Plan House Enrolled Act 1678 A Pragmatic Approach Governor Mitch Daniels July 16, 2007 Indiana s Fiscal Health is Good First Back-to-Back Balanced Budget in Eight Years $1,000.0 Revenue
More informationAddressing Substance Abuse To Improve Well-Being in Child Welfare Systems Current Trends, Continuing Challenges
Addressing Substance Abuse To Improve Well-Being in Child Welfare Systems Current Trends, Continuing Challenges Three Branch Institute on Child Well-Being July 1, 2014 Sid Gardner, MPA Drugs of the Decades
More informationMost common metabolic disorders in childhood. Neonatal screening and diagnostic approach to the. Inborn errors of metabolism (IEM)
Department of Pediatrics and Developmental Disorders Medical University of Bialystok Most common metabolic disorders in childhood. Neonatal screening and diagnostic approach to the inborn errors of metabolism
More informationAttachment 1. Newborn Screening Program Description
Attachment 1 Newborn Screening Program Description The core mission of Texas Newborn Screening Program is to save children s lives through the early detection of life-threatening disorders. 34 Newborn
More informationPrecision Medicine. Wendy Chung, MD PhD Director of Clinical Genetics Columbia University
Precision Medicine Wendy Chung, MD PhD Director of Clinical Genetics Columbia University What is precision medicine? Providing the right treatment for the right patient at the right time and engaging the
More informationApplication to be an additional provider for existing test on the NHS Directory of Molecular Genetic Testing Additional Provider form
Application to be an additional provider for existing test on the NHS Directory of Molecular Genetic Testing Additional Provider form Disease: Gene: Cystic Fibrosis (CF) (carrier testing in reproductive
More informationCDC activities Autism Spectrum Disorders
CDC activities Autism Spectrum Disorders Georgina Peacock, MD, MPH Centers for Disease Control and Prevention National Center on Birth Defects and Developmental Disabilities The findings and conclusions
More informationPULMONARY SURFACTANT, ALPHA 1 ANTITRYPSIN INHIBITOR DEFICIENCY, AND CYSTIC FIBROSIS DR. NABIL BASHIR BIOCHEMISTRY/RESPIRATORY SYSTEM
PULMONARY SURFACTANT, ALPHA 1 ANTITRYPSIN INHIBITOR DEFICIENCY, AND CYSTIC FIBROSIS DR. NABIL BASHIR BIOCHEMISTRY/RESPIRATORY SYSTEM Pulmonary surfactant Pulmonary surfactant is (phospholipoprotein) complex
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 Genetic Causes of Hypothyroidism 1. Loss of function mutations in TSHR cause thyroid
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 informationHuman Genetic Diseases (non mutation)
mutation) Pedigrees mutation) 1. Autosomal recessive inheritance: this is the inheritance of a disease through a recessive allele. In order for the person to have the condition they would have to be homozygous
More informationScreening Newborns for Congenital Disorders
Screening Newborns for Congenital Disorders Gary L. Hoffman, BS; Ronald H. Laessig, PhD ABSTRACT The Newborn Screening Laboratory at the Wisconsin State Laboratory of Hygiene (WSLH) tests all newborn babies
More informationNCQA did not add new measures to Accreditation 2017 scoring.
2017 Accreditation Benchmarks and Thresholds 1 TO: Interested Organizations FROM: Patrick Dahill, Assistant Vice President, Policy DATE: August 2, 2017 RE: 2017 Accreditation Benchmarks and Thresholds
More informationRespiratory Pharmacology: Treatment of Cystic Fibrosis
Respiratory Pharmacology: Treatment of Cystic Fibrosis Dr. Tillie-Louise Hackett Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Associate Head, Centre of Heart
More informationPathophysiology of the Phenylketonuria
Problem 4. Pathophysiology of the Phenylketonuria Readings for this problem are found on pages: 79-82, 84, 85-6, 945-6 and 1019 of your Pathophysiology (5 th edition) textbook. (This problem was based
More informationEnabling CF Therapeutic Development
Enabling CF Therapeutic Development PRESTON W. CAMPBELL, III, M.D. Executive Vice President for Medical Affairs No Disclosures Cystic Fibrosis In 1955 In 1955 most children with CF did not live long enough
More informationNewborn Screening for Cystic Fibrosis
Newborn Screening for Cystic Fibrosis Three States Experience with IRT/IRT/DNA Marci Sontag PhD, Norm Brown, Dan Wright, Art Cowes, Rachel Lee, Susan Tanksley Colorado School of Public Health and Children
More informationTrends in Lung Cancer Morbidity and Mortality
Trends in Lung Cancer Morbidity and Mortality American Lung Association Epidemiology and Statistics Unit Research and Program Services Division November 2014 Table of Contents Trends in Lung Cancer Morbidity
More informationQuarterly Hogs and Pigs
Quarterly Hogs and Pigs ISSN: 9- Released December 22,, by the National Agricultural Statistics Service (NASS), Agricultural Statistics Board, United s Department of Agriculture (USDA). United s Hog Inventory
More informationQuarterly Hogs and Pigs
Quarterly Hogs and Pigs ISSN: 9- Released December 23,, by the National Agricultural Statistics Service (NASS), Agricultural Statistics Board, United s Department of Agriculture (USDA). United s Hog Inventory
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 informationStates with Authority to Require Nonresident Pharmacies to Report to PMP
States with Authority to Require Nonresident Pharmacies to Report to PMP Research current through May 2016. This project was supported by Grant No. G1599ONDCP03A, awarded by the Office of National Drug
More informationMedical Advisory Board. reviews medical issues for licensure regarding individual drivers. medical conditions. not specified. reporting encouraged,
State Reporting Regulations for Physicians Adapted from the Physician s Guide to Assessing and Counseling Older Drivers 44 and Madd.org 45 State Physician/Medical Reporting (NOTE MERGED CELLS) Mandatory,
More informationThe 2004 National Child Count of Children and Youth who are Deaf-Blind
The 2004 National Child Count of Children and Youth who are Deaf-Blind NTAC The Teaching Research Institute Western Oregon University The Helen Keller National Center Sands Point, New York The National
More informationMutational and phenotypical spectrum of phenylalanine hydroxylase deficiency in Denmark
Clin Genet 2016: 90: 247 251 Printed in Singapore. All rights reserved Short Report 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd CLINICAL GENETICS doi: 10.1111/cge.12692 Mutational and
More informationcertain genotypes known to be associated with genetic disease or a predisposition to genetic disease
DARYL L. THULL, MS 1 Good morning. So I thought that it would be helpful to sort of go back and see what population screening for genetic disease, sort of what the definition is. And it's testing to identify
More information