Download Hangzhou Pagon GeneTests 10-12-07-BP-ca

Genetic Testing:
The Clinician’s Perspective
Roberta A. Pagon, MD
Professor, Pediatrics
University of Washington, Seattle
Third Annual Short Course on Medical and Laboratory
Applications of Genetics and Genomics
Hangzhou, China
November 1, 2007
Genetic Testing
• Molecular genetic testing in
patient care
• GeneTests
• Essential elements of testing for
clinicians
Genetic Testing
• Molecular genetic testing in
patient care
• GeneTests
• Essential elements of testing for
clinicians
Uses of Molecular Genetic Testing
in 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)
65 y
33 y
65 y
28 y
40 y
Proband
HNPCC
50% risk
Indeterminate risk
15 y
13 y
12 y
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
Genetic Testing
• Molecular genetic testing in clinical
practice: BASIC PRINCIPLES
• GeneTests
• Clinical testing: Essential elements for
clinicians
www.genetests.org
Information resource for healthcare providers to
help integrate genetic services into patient care
Located at
University of Washington
Seattle, WA
Funded by
National Institutes of Health
• 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
 1160 clinics
• 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
GeneReviews: Search by Disease
HNPCC
GeneReviews: Disease Search Result
Clinical Testing
Research Testing
GeneReview
Consumer Oriented Resources
GeneReviews: Search by Title
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 Callosum
Hereditary Neuropathy with Liability to Pressure Palsies
Hereditary Non-Polyposis Colon Cancer
Hereditary Sensory Neuropathy Type I
Hereditary Spastic Paraplegia Overview
GeneReviews Content
Summary
Diagnosis
Clinical Description
Differential Diagnosis
Management
Genetic Counseling
Molecular Genetics
Resources
References
GeneReviews
Summary
One paragraph on:
Disease characteristics
Diagnosis/testing
Management
Genetic counseling
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
Natural History
What are the clinical findings in this
disorder?
What happens over time to people who have
this condition?
How does the disease progress?
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
• Molecular genetic testing in clinical
practice: BASIC PRINCIPLES
• GeneTests: EASY TO USE
• Essential elements of genetic testing
for clinicians
Genetic Testing
• Molecular genetic testing in clinical
practice: BASIC PRINCIPLES
• 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
Genetic Testing:
Essential Elements for Clinicians
• 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
Genetic Testing:
Essential Elements for Clinicians
Being developed in the US by the
Collaboration, Education, Test Translation
(CETT) Program
www.cettprogram.org
Genetic Testing
• Molecular genetic testing in clinical
practice: BASIC PRINCIPLES
• GeneTests: EASY TO USE
• Essential elements of genetic testing
for clinicians: HARD TO DO
Genetic Testing
• Molecular genetic testing in clinical
practice: BASIC PRINCIPLES
• 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
Staff
Principal Investigator
GeneReviews
Editor-in-Chief
Roberta A Pagon, MD
Associate Editors
Thomas D Bird, MD
Cynthia R Dolan, MS
Gerald L Feldman, MD, PhD
Richard JH Smith, MD, PhD
Karen Stephens, PhD
Assistant Editors
Suzanne B Cassidy, MD
Mary Beth P Dinulos, MD
Amy Lawson Yuen, MD, PhD
Managing Editor
Monica Smersh
Online Production
Editor
Update Manager
Editorial Assistants
Miriam Espeseth, MA
Roberta A Pagon, MD
Directories
Genetic Counselors
Cynthia R Dolan, MS
Roberta Spiro, MA
Laboratory Directory
Coordinator
Gina McCullough Grohs
Resources
Resources Liaison
Technical Support
Database
Administrator
Ellen Terry
Carla Gifford
Candace Street
Kathi Marymee, MS
Systems
Administrators
Sergey Mikhaylov, MS
Michael Kortas
Brad Willson