1. How do we get started?
   We strongly encourage applicants to contact Andy Faucett, CETT Program Coordinator (info@CETTProgram.org or 404-727-4510), early in the process to obtain assistance as the proposal is developed.

2. What if the advocate group and researcher are committed, but don’t have a laboratory?
   Six laboratories in the National Laboratory Network (NLN) for Rare Disease Genetic Testing are experienced clinical laboratories that are ready to work with CETT Program applicants and become active participants in a CETT Collaborative Group. The CETT Program Coordinator can put applicants in touch with an NLN laboratory.

3. What if the collaborative group has a laboratory and a researcher group, but there is not an advocate group?
   The CETT Program has affiliations with the Genetic Alliance (GA) and the National Organization for Rare Disorders (NORD) to help CETT Program applicants. Contact the CETT Program Coordinator. The CETT Program also has brought together a group of experienced patient advocates (CETT Program Advocacy Mentors) who will act as mentors for each collaborative group. Some CETT Collaborative Groups have partnered with an umbrella advocacy group and a single family when a specific advocacy organization does not exist.

4. Who is responsible for each part of a test plan?
   The CETT Program Team realizes that each CETT Program Collaborative Group may divide the responsibilities of test development, educational material development, etc., differently. The application should clearly identify who is responsible for each part of the process and briefly explain their qualifications.

5. How do we learn more about the requirement to collect the clinical and genotype information?
   It is likely that for each test the information that should be collected and that can be collected efficiently may be different. Contact the National Center for Biotechnology Information (NCBI) (info@ncbi.nlm.nih.gov) early for assistance in this area. Each CETT Collaborative Group is encouraged to develop a plan that works best for them. It may be appropriate to have more than one way to collect clinical information. For example, the laboratory sample could be collected through the patient Web site or directly from the clinician. In deciding who should house and provide access to the information, Institutional Review Board (IRB) and patient confidentiality issues should be considered.

6. How should the budget be developed?
   Based on discussions with laboratories currently performing rare genetic testing, the CETT Program Team projects that a working budget of approximately $1,000 per amplicon (one or more exons) will be used as a guide for molecular tests. In addition, approximately $1,000 is available to support the development of educational materials. These figures include overhead and indirect costs. It is expected that the laboratory (institution) and/or the patient advocate group will contribute to the cost of test translation.

7. Are there unique challenges for a rare disease testing laboratory?
   Discussions at the Rare Disease meetings in May 2004 and September 2005 highlighted issues that may be challenging for laboratories performing low volume rare disease tests. Comments and recommendations from the NLN laboratories are available through the CETT Program Coordinator. (Note: Please check back; comments and issues to consider will be continuously updated from input from the NLN laboratories, other laboratories that have participated in rare disease test translation, and other laboratories currently performing rare disease testing.)

8. How can the CETT Collaborative Group guarantee the availability of testing for 5 years?
   One of the differences between a research laboratory and a clinical laboratory is the commitment to provide testing services on a regular, long-term basis. If for some reason a CETT Collaborative Group is not able to provide testing that is still needed for the full 5 years, it should be committed to transition the test to another clinical laboratory that can offer the same level of service.

9. How does the CETT Program define the various types of clinical tests?
   The CETT Program uses the following definitions from GeneTests:

   • Diagnostic testing: Testing of a symptomatic individual that is the only means by which the diagnosis of a specific genetic disorder can be established (e.g., identification of a CAG trinucleotide expansion greater than a certain size in a person suspected of having Huntington disease establishes the diagnosis)

   • Confirmatory diagnostic testing: Testing of a symptomatic individual that is used to establish the diagnosis of a specific genetic disorder when the clinical findings are equivocal

   • Carrier testing: Testing usually of an asymptomatic individual to determine if a single copy of a mutation for an autosomal recessive or X-linked recessive disorder is present

   • Predicative testing: Testing of an asymptomatic individual with a family history of a genetic disorder who is at risk of developing the disorder

   • Prognostic testing: When strong genotype-phenotype correlations exist, establishing the genotype of a symptomatic individual in order to determine the probability that certain phenotypic features will appear over time

   • Prenatal diagnosis: Testing performed during pregnancy to determine if a fetus is affected with a particular disorder

   • Preimplantation genetic diagnosis (PGD): Testing one cell removed from an early embryo conceived by in vitro fertilization for a mutation(s) for which it is specifically at increased risk; then transferring to the mother's uterus only those embryos determined not to have inherited the mutation(s) in question

10. Does the CETT Collaborative Group have to commit to developing a GeneReview?
    Yes, one of the goals of the CETT Program is to have a GeneReview available for each condition that is funded for test translation. This is not due at the time of application but should be completed within the first 12 months of testing. Below is the GeneReview outline. Items starred (*) below may be optional in the initial educational material developed but would be included in the GeneReview.
    • Diagnosis
      • Clinical Diagnosis
      • Molecular Genetic Testing
        • Gene(s)
        • Locus (loci)
        • Molecular genetic testing: clinical uses
        • Molecular genetic testing: clinical methods
      • Test Interpretation Issues
      • Testing Strategy for a Proband
      • Genetically Related Allelic Disorders
    • Clinical Description
      • Natural History
      • Genotype-Phenotype Correlations
      • *Penetrance
      • *Anticipation
      • Nomenclature (old names, etc.)
      • *Prevalence
    • Differential Diagnosis
    • Management
      • Evaluations at Initial Diagnosis
      • *Treatment of Manifestations
      • *Prevention of Primary Manifestations
      • *Prevention of Secondary Complications
      • *Surveillance
      • Testing of Relatives at Risk
      • Agents/Circumstances to Avoid
      • *Therapies under Investigation
      • Other
    • Genetic Counseling
      • Mode of Inheritance
      • Risk to Family Members
        • Parents of a Proband
        • Siblings of a Proband
        • Offspring of a Proband
        • Other family members
      • Carrier Detection
      • *Related Genetic Counseling Issues
        • DNA banking
      • Prenatal Testing
    • Molecular Genetics
      • Table: Gene symbol, Chromosomal locus, Protein name
      • *Molecular Genetic Pathogenesis
        • Normal allelic variants (#exons, #polymorphisms)
        • Pathologic allelic variants
        • Normal gene product
        • Abnormal gene product
      • Resources
      • *References
        • Statements & Guidelines Regarding Genetic Testing
        • Literature Cited
        • Suggested Reading (no more than six articles, each 3 years old or less)
      • Author Information

11. Does the CETT Collaborative Group have to have all the educational materials ready with the application?
    No, the CETT Program understands the amount of work involved in developing effective educational materials. You should have a plan that clearly indicates who is responsible for what. If this is the first time for the Collaborative Group to offer rare genetic disease testing, the CETT Program team would like to see an example of what you plan to provide. Visit the CETT Program Web site for examples of educational materials on laboratory testing.

12. What are the most important issues to discuss in the educational material provided?
    

    • Why did my child (or I) have this test?
    • What do the results of this test mean for my child’s (or my) health?
    • What do the test results mean for other members of my family?
    • Where can I find a healthcare professional who understands this condition and can help me understand the results of testing?
    • With whom should I share this information?
    • With whom should I not share this information?
    • Where can I find more information?
    
    Examples of effective educational material can be found on the CETT Program Web site. (Check back; we will be adding examples on an ongoing basis.)

Email Andy Faucett with questions.