1. Genetic Testing in Human: The Clinician’s Perspective http://www. ncbi

2. Genetic Testing in Human
Molecular genetic testing in patient care
GeneTests
Essential elements of testing for clinicians

3. Uses of Molecular Genetic Testing
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

4. Molecular Genetic Testing: a.Medical Care
Diagnostic testing in symptomatic persons
Predictive testing in asymptomatic persons when treatment is available

5. Medical Care: a1.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)

6. Medical Care: a2.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)

7. 33 y Proband HNPCC 50% risk Indeterminate risk 28 y 65 y 40 y 13 y

8. Molecular Genetic Testing: b.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

9. Genetic Testing
Molecular genetic testing in clinical practice: BASIC PRINCIPLES
GeneTests
Clinical testing: Essential elements for clinicians

12. GeneReviews: “User manual” for genetic testing for specific diseases
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
Illustrated Glossary: Genetic counseling and testing terms

13. Molecular genetic testing:
Testing used in patient care must be done in “clinical” laboratories, not research laboratories
Clinical laboratories have to meet standards set by federal law (“BHP”)

14. 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

15. GeneReviews: Search by Disease

16. GeneReviews: Search by Disease
HNPCC

17. GeneReviews: Disease Search Result
Clinical Testing
Research Testing
GeneReview
Consumer Oriented Resources

18. GeneReviews: Search by Title

19. GeneReviews: Search by Title

20. 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

22. GeneReviews Content Summary Diagnosis Clinical Description
Differential Diagnosis
Management
Genetic Counseling
Molecular Genetics
Resources
References

23. GeneReviews Summary One paragraph on: Disease characteristics
Diagnosis/testing
Management
Genetic counseling

24. GeneReviews Diagnosis
Clinical Diagnosis
Testing
Molecular genetic testing
Testing strategy (Order in which to use all the testing described above for diagnosis)

25. 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?   

26. GeneReviews Differential Diagnosis
What other conditions are similar to this condition?

27. 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

28. GeneReviews Genetic Counseling
Risk to Family Members
Parents of a proband
Sibs of a proband
Offspring of a proband
Prenatal Testing

29. Genetic Testing
Molecular genetic testing in clinical practice: BASIC PRINCIPLES
GeneTests: EASY TO USE
Essential elements of genetic testing for clinicians

30. 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

31. 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?

32. 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

33. 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

34. Thank you ! http://www.ncbi.nlm.nih.gov/sites/GeneTests/