Genetic Testing for Wilson Disease Melissa Dempsey, M.S., CGC The University of Chicago Genetic Services Laboratory July 17, 2010.

Slides:



Advertisements
Similar presentations
Lecture 45 Prof Duncan Shaw. Applications - finding genes Currently much interest in medical research, in finding the genes causing disease Sometimes.
Advertisements

Implications of Consanguinity for Routine Diagnostic Testing and Development of Specialist Services Teresa Lamb Clinical Scientist Leeds DNA Laboratory.
Clinical background: Patient RM, YoB 1966 Her family were originally referred because of a history of breast and ovarian cancer. BRCA testing found a missense.
THE SCIENCE OF PROGRESS Genetics and Biotechnology Module Lesson I: Meet the Millers.
Diagnostic mtDNA analysis in body fluids other than blood Sarah Ball 1, George Gray 1, Ros Quinlivan 3, Paul Brown 4, Chris Hendriksz 2 Birmingham Children’s.
Genetics and genomics for healthcare © 2014 NHS National Genetics and Genomics Education Centre Why is genetics relevant to.
Diagnosing Niemann Pick disease, Type C MODIFIED FROM A SLIDE SHOW Developed by the Sanford PROMISE The Sanford PROMISE Program for the Midwest Initiative.
NOTES 24 – Genetic Disorders and Hereditary Diseases
6.2 Human Genetic Disorders
Issues in Genetic Testing: Real versus Not-so-Real Roberta A Pagon, MD Principal Investigator, GeneTests Professor, Pediatrics University of Washington.
Genetic Counseling & Alport Syndrome
Enhanced Prenatal Screening Program
Meet the Gene Machine Basic Genetics & Background on Genetic Testing.
Genetic Counseling & Genetic Testing Katelyn Meadows & Betty Hagerman.
HUMAN GENETIC DISORDERS Chapter 4, Lesson 2. Causes of Genetic Disorders  Some genetic disorders are caused by mutations in the DNA genes.  Other disorders.
Human Heredity and Genetic Disorders
6-2 Human Genetic Disorders
Human genetic disorders
The genetic counsellor When there is a possibility that a couple may have a child with a genetic disease, they may be referred to a genetic counsellor.
Careers in Genetic Counseling
By: Lauren Filice Jasmine Mateo Monica La Borde Wilson Disease.
Wilson's Disease hepatolenticular degeneration Copper storage disease Wilson's disease causes the body to take in and keep too much copper. The copper.
Genetic/Chromosomal Disorder Presentation By: Brian Smith.
By Ivy Poon, Diana Jackson, and Annaliese Yostpile
Family members often share a strong physical resemblance.
Careers in Psychology Florida State University
 There are about 900 tests available for discovering genetic abnormalities.  Reasons for such testing include: › Finding possible genetic diseases in.
Chromosomes, Karyotypes, and Pedigrees Oh My! 14.1/14.2 1copyright cmassengale.
Genetic Alterations of TP53 Gene in Brain Astrocytic Tumours Methodology Θ Eighty-three brain tumor biopsies were collected and used in this study. Thirty.
Pregnancy & Newborn Screening Developments Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD)
POSITIONAL CLONING TWO EXAMPLES. Inheritance pattern - dominant autosomal Entirely penetrant and fatal Frequency - about 1/10,000 live births Late onset.
Cystic Fibrosis: A Review for Healthcare Providers
GENETIC TESTING: WHAT DOES IT REALLY TELL YOU? Lori L. Ballinger, MS, CGC Licensed Genetic Counselor University of New Mexico Cancer Center.
Example of Medical Record Elements
Lesson 3 Family members often share a strong physical resemblance. What inherited characteristics are visible in this family? Heredity and Genetics.
Hemophilia A By Saad Mukaty. Definition of Hemophilia  Hemophilia (A) is a rare disorder in which blood doesn’t clot normally because it lacks important.
Laboratory methods look at your genes, which are DNA instructions you inherit from a biological mother and father Genetic tests can identify increased.
Lesson 3 2/23/12 Heredity & Genetics Name a few traits that you inherited from a family member? What family member did you inherit the trait from?
What is a Pedigree… And Nooooo it’s not Dogfood.
SICKLE CELL ANEMIA Omar and Yassin.
CHAPTER 9 Patterns of Inheritance Part 3. Human Genetic Analysis  Since humans live under variable conditions, in different places, and have long life.
Human Genetics and Genetic Technology Using Genetic InformationUsing Genetic Information.
You are the Counselor. What skills do I need to be genetic counselor? Master’s degree in Genetic Counseling Strong person-to-person communication skills.
Private pay, physician ordered genetic testing Developed by Dr. Judith Allanson, Ms. Shawna Morrison and Dr. June Carroll Last updated November 2015.
Understanding Genetic Testing
Genetic disorders can be due to any of the following factors: A. Monogenetic Disorders: Caused by a mutation in a single gene 1. Autosomal recessive alleles:
Human Genetic Disorders Notes. What causes genetic disorders? Mutations, or changes in a person’s DNA.
HUNTINGTON’S DISEASE Neil Madadi. WHAT IS HUNTINGTON’S DISEASE?  It is an autosomal dominant inherited disease. Meaning that only one copy of the altered.
What is a Pedigree… And Nooooo it’s not Dogfood. Biology I Searcy Ninth Grade Center.
Human Genomics Higher Human Biology. Learning Intentions Explain what is meant by human genomics State that bioinformatics can be used to identify DNA.
DIAGNOSIS OF WILSON’S DISEASE – A 20-YEAR AUDIT Geetha Rathnayake 1, Mirette Saad 2, Kay Weng Choy 1, James CG Doery 1,3 1 Monash Pathology, Monash Medical.
Human Genetic Disorders Human Genetics and Genetic Technology.
BY: MARIA BEECHER Wilson’s Disease. Intro Samuel Alexander Kinnier Wilson 1 in 30,000 people Rare genetic disease  Build up of copper Affected organs.
Genes in Life is a place to learn about all the ways genetics is a part of your life. On this site you will learn:   How.
Hereditary Cancer Predisposition: Updates in Genetic Testing
What Causes Wilson Disease? Wilson disease is caused by mutations in the ATP7B gene. This gene makes an enzyme that is involved in copper transport.
Characterization of VHL promoter variants in patients suspected of Von Hippel Lindau Saleh Albanyan, Rachel Giles, Raymond H Kim, MD/PhD Division of.
Li-Fraumeni Syndrome Wendy Kohlmann, MS, CGC
Genetic Testing Result Means. Before Genetic Testing  The result of genetic testing can be life changing.  It is important for patients and their families.
Patient VB Li-Fraumeni Syndrome.
Content and Labeling of Tests Marketed as Clinical “Whole-Exome Sequencing” Perspectives from a cancer genetics clinician and clinical lab director Allen.
ALBINISM By: Melissa H.
STEVE S. SOMMER, M.D., Ph.D.  Mayo Clinic Proceedings 
Genetics and Breast Cancer Adelphi 2018 Educational Forum Sharona Cohen, MS, CGC Certified Genetic Counselor Northwell Health.
Basic Genetics & Background on Genetic Testing
Cells and Heredity Chapter 5: Humans Genetics and Genetic Technology
Class Notes #8: Genetic Disorders
Jeopardy Prenatal Care Genetic Disorders Hodge Podge PCR
Following Patterns of Inheritance in Humans
Breast Cancer BRCA testing protocol
Presentation transcript:

Genetic Testing for Wilson Disease Melissa Dempsey, M.S., CGC The University of Chicago Genetic Services Laboratory July 17, 2010

What Causes Wilson Disease? Wilson disease is caused by mutations in the ATP7B gene. Wilson disease is caused by mutations in the ATP7B gene. This gene makes an enzyme that is involved in copper transport. This gene makes an enzyme that is involved in copper transport. When the enzyme is mutated (not working properly) copper accumulates in the liver and brain and becomes toxic. When the enzyme is mutated (not working properly) copper accumulates in the liver and brain and becomes toxic.

How Does it Run in Families? Wilson disease is inherited in an autosomal recessive pattern. Wilson disease is inherited in an autosomal recessive pattern. Affected individuals have mutations in both copies of ATP7B Affected individuals have mutations in both copies of ATP7B Carriers (mutation in only one copy) do not have symptoms Carriers (mutation in only one copy) do not have symptoms

How Does it Run in Families? Ww wwWw WW

Current US Clinical Testing for Wilson Disease The University of Chicago The University of Chicago Ambry Genetics Ambry Genetics Boston University School of Medicine Boston University School of Medicine Mayo Clinic Mayo Clinic Prevention Genetics Prevention Genetics Seattle Children’s Hospital Seattle Children’s Hospital University of Oklahoma Health Sciences Center University of Oklahoma Health Sciences Center

Our Test... Full gene sequencing of coding region of atp7b (21 exons) Full gene sequencing of coding region of atp7b (21 exons) –Cost: $2025 –TAT: weeks

DNA extraction Process of getting DNA from a blood, saliva, or other body tissue. Process of getting DNA from a blood, saliva, or other body tissue. s/extraction/ s/extraction/ s/extraction/ s/extraction/ Process of getting DNA from a blood, saliva, or other body tissue. Process of getting DNA from a blood, saliva, or other body tissue. s/extraction/ s/extraction/ s/extraction/ s/extraction/

Targeting ATP7B Targeting ATP7B Need to PCR amplify each exon (21) of ATP7B before sequencing Need to PCR amplify each exon (21) of ATP7B before sequencing Ex 1Ex 2Ex 3Ex 4Ex 5Ex 6Ex 7Ex 8Ex 9

PCR Amplification Reproduce only the parts of DNA (exons of ATP7B) that you are interested in. Reproduce only the parts of DNA (exons of ATP7B) that you are interested in. 2T8fVk 2T8fVk 2T8fVk 2T8fVk

DNA Sequencing Reading the DNA code within the ATP7B gene to look for any changes. Reading the DNA code within the ATP7B gene to look for any changes. Cycle sequencing animation Cycle sequencing animation HhvecM HhvecM HhvecM HhvecM

Ordering Testing A physician must order the test A physician must order the test We recommend that a geneticist or genetic counselor be involved in ordering testing We recommend that a geneticist or genetic counselor be involved in ordering testing –Finding a genetics clinic or GC—   They will fill out the appropriate paperwork and arrange for blood sample to be sent to The University of Chicago They will fill out the appropriate paperwork and arrange for blood sample to be sent to The University of Chicago

Ordering Testing Test report will be faxed to referring physician Test report will be faxed to referring physician Geneticist/GC can explain results and implications to family Geneticist/GC can explain results and implications to family Questions? —Please contact me! Questions? —Please contact me! –Melissa Dempsey, MS The University of Chicago

Insurance/Billing The University of Chicago will bill your insurance company or accept payment by check or credit card. The University of Chicago will bill your insurance company or accept payment by check or credit card. All insurance companies are different, but most of them should cover at least part of the cost of testing. All insurance companies are different, but most of them should cover at least part of the cost of testing. CPT (Current Procedural Terminology) codes: CPT (Current Procedural Terminology) codes: –Insurance companies use these codes to define the method of testing. –For ATP7B testing: 83891, x 4, x 9,

Possible Results: 2 mutations detected: –confirms diagnosis of Wilson Disease. –allows for easy testing of other family members, who may want testing.

Possible Results: 1 mutation detected: –does not confirm or rule out Wilson Disease  patient may have 2nd mutation that wasn’t detected  Patient may be a carrier of WD and have some other reason for their symptoms  ~1/90 individuals are carriers of WD.

Possible Results: No mutation detected: –does not rule out the diagnosis. –~98% of people with WD will have mutations identified. –If diagnosis is doubtful, a negative result leans against the diagnosis, and other possible diagnoses should be considered.

Possible Results: Variant of unknown significance: –A small number of people will have a change in the gene, but we do not know what the change means –May recommend testing other family members to try to figure it out.

Case #1 12 year old female with abnormal copper levels Exon 6 c.1934T>G (p.M645R)

Case #1 12 year old female with abnormal copper levels Exon 18 c.3809A>G c.3809A>G (p.N1270S)

Case #2 12 year old male with atypical symptoms Single mutation detected Exon 6 c.1877G>C (p.G626A)