genetic testing: the clinician’s perspective roberta a. pagon, md professor, pediatrics university...

Genetic Testing: The Clinician’s Perspective

Roberta A. Pagon, MDProfessor, Pediatrics

University of Washington, Seattle

Third Annual Short Course on Medical and Laboratory Applications of Genetics and Genomics

Hangzhou, ChinaNovember 1, 2007

Genetic Testing

• Molecular genetic testing in patient care

• GeneTests

• Essential elements of testing for clinicians

Uses of Molecular Genetic Testingin the United States

• To help physicians provide the best medical care for a patient with an inherited disorder

• To help a person with an inherited disorder make informed personal decisions

Molecular Genetic Testing:Medical Care

• Diagnostic testing in symptomatic persons

• Predictive testing in asymptomatic persons when treatment is available

Medical Care: Symptomatic Person

• Establish a diagnosis (e.g., Huntington disease: HD gene testing is the only way to make the diagnosis with certainty)

• Confirm a diagnosis (e.g., HNPCC: MLH1/MSH2 testing in a person who does not quite meet Amsterdam criteria)

Medical Care: At-risk Asymptomatic Person

Predictive testing: Identify family members who have the disease-causing mutation before symptoms appear so that they can be monitored for early signs of the disease and treated promptly to reduce morbidity and mortality (e.g., HNPCC)

33 y 28 y

65 y65 y

Indeterminate risk

13 y 12 y15 y

50% risk

HNPCC

40 y

Proband

Molecular Genetic Testing:Personal Decision-making*

• Carrier testing: Autosomal recessive disorders

• Predictive testing: No treatment available

• Prenatal diagnosis/Preimplantation genetic diagnosis (PGD)

*Results of testing do not help medical care

Genetic Testing

• Molecular genetic testing in clinical practice: BASIC PRINCIPLES

• GeneTests

• Clinical testing: Essential elements for clinicians

www.genetests.org

Funded by National Institutes of Health

Located atUniversity of WashingtonSeattle, WA

Information resource for healthcare providers to help integrate genetic services into patient care

1160 clinics

• GeneReviews: “User manual” for genetic testing for specific diseases

405 GeneReviews One new Review added each week

• Laboratory Directory: “Yellow Pages” of genetics labs

~610 Clinical and research laboratories ~1460 Inherited diseases ~1180 clinical tests ~280 research only

• Clinic Directory: “Yellow Pages” of genetic services

• Illustrated Glossary: Genetic counseling and testing terms

Molecular genetic testing:United States

• Testing used in patient care must be done in “clinical” laboratories, not research laboratories

• Clinical laboratories have to meet standards set by federal law (“CLIA”)

• Non-US laboratories are used when testing is not available in the US

Molecular genetic testing:China

• Testing for patient care is only available through research laboratories

• Laboratories outside of China cannot be used for testing yet

GeneTests Laboratory Directory

• Useful in US to identify US and non-US clinical laboratories testing for specific inherited diseases

• Not so useful yet in China

GeneReviews

• Useful to all clinicians regardless of availability of molecular genetic testing

• Provide to non-expert clinicians information on the diagnosis, management and genetic counseling of patients with inherited disorders and their families

• Expert-authored, peer-reviewed, updated regularly

GeneReviews: Search by Disease

HNPCC

GeneReviews: Search by Disease

GeneReviews: Disease Search Result

Clinical Testing

Research Testing

GeneReview

Consumer Oriented Resources

GeneReviews: Search by Title

GeneReviews: HNPCC

Disease search result: Select Reviews button

Title search result: Select HNPCC from the list

Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus CallosumHereditary Neuropathy with Liability to Pressure PalsiesHereditary Non-Polyposis Colon CancerHereditary Sensory Neuropathy Type IHereditary Spastic Paraplegia Overview

GeneReviews Content

Summary

Diagnosis

Clinical Description

Differential Diagnosis

Management

Genetic Counseling

Molecular Genetics

Resources

References

GeneReviewsSummary

Disease characteristics

Diagnosis/testing

Management

Genetic counseling

One paragraph on:

GeneReviews Diagnosis

Clinical Diagnosis

Testing

Molecular genetic testing

Testing strategy (Order in which to use all the testing described above for diagnosis)

GeneReviews Clinical Description

What are the clinical findings in this disorder?

What happens over time to people who have this condition?

How does the disease progress?

Natural History

GeneReviews Differential Diagnosis

What other conditions are similar to this condition?

GeneReviews Management

Evaluations Following Initial Diagnosis

Treatment of Manifestations

Prevention of Primary Manifestations

Prevention of Secondary Complications

Surveillance

Agents/Circumstances to Avoid

Testing of Relatives at Risk

Therapies Under Investigation

GeneReviews Genetic Counseling

Risk to Family Members • Parents of a proband • Sibs of a proband • Offspring of a proband

Prenatal Testing

Genetic Testing


• GeneTests: EASY TO USE

• Essential elements of genetic testing for clinicians

Genetic Testing: Essential Elements for Clinicians

• Educational materials about the disease and the test

• Test result report forms that explain the test and the patient’s test result

• Collection of data on phenotype and genotype


• Sound easy, but are VERY hard to do

• In general, US laboratories do not provide the essential elements

RECOMMEND: Have essential elements in place before offering clinical testing

Essential Elements:Educational Materials

• What is the test?

• What is the test used for?

• Who should be tested?

• What does a positive test result mean for the patient?

• What does a negative test result mean for the patient?

Essential Elements: Test Result Report Forms

• Clinical Indication: Why is the test being performed?

• Results: Normal, abnormal, uncertain

• Interpretation: What do results mean for this patient?

• Limitations: What can’t the test do?

• Suggestions for test result clarification: Testing other family members, other tests to do

• Test methods: How was this test performed?

• Resources: Links or citations to help the clinician understand more about the disease or test

• References: Literature citations

Genetic Testing: Data Collection

• A one page (electronic) phenotype data collection form to be filled in by the clinician at the time the test is ordered. Must be anonymous to protect the patient.

• Central database for phenotype data and genotype data when testing is completed


Being developed in the US by the Collaboration, Education, Test Translation (CETT) Program

www.cettprogram.org

Genetic Testing


• GeneTests: EASY TO USE

• Essential elements of genetic testing for clinicians: HARD TO DO

Thank you !

For your kind invitation to visit your beautiful city and to speak at this

stimulating conference

Roberta A Pagon, MD

Thomas D Bird, MD Cynthia R Dolan, MS Gerald L Feldman, MD, PhDRichard JH Smith, MD, PhDKaren Stephens, PhD

Suzanne B Cassidy, MDMary Beth P Dinulos, MDAmy Lawson Yuen, MD, PhD

Monica Smersh

Miriam Espeseth, MA

Ellen Terry

Carla GiffordCandace Street

Editor-in-Chief

Associate Editors

Assistant Editors

Managing Editor

Online ProductionEditor

Update Manager

Editorial Assistants

Genetic Counselors

Laboratory DirectoryCoordinator

Cynthia R Dolan, MSRoberta Spiro, MA

Gina McCullough Grohs

Database Administrator

SystemsAdministrators

Sergey Mikhaylov, MS

Michael KortasBrad Willson

Staff

GeneReviews

Principal Investigator Roberta A Pagon, MD

Directories

Technical Support

Resources

Resources Liaison Kathi Marymee, MS

genetic testing: the clinician’s perspective roberta a. pagon, md professor, pediatrics university...

Documents

china testing

carrier testing

results of testing

testing terms

mlh1msh2 testing

united states testing

hd gene testing

medical care slide