William A. Gahl, MD, PhD

1. William A. Gahl, MD, PhD Clinical Director, National Human Genome Research Institute Director, Intramural Program, NIH Office of Rare Diseases

2. Molecular Diagnostics of Rare Diseases CLIA-certified labs do not offer testing. Setup is expensive. Disorders are not common enough to make money. Research labs without CLIA certification cannot provide results to patients. This national issue is also important for intramural researchers in the NHGRI.

3. Prototypic Solution - for Intramural NHGRI NHGRI and the Office of Rare Diseases co-sponsors molecular diagnostics of specific disorders studied by intramural NHGRI. Funding of CLIA-certified labs specifically to set up the diagnostics: Labs are private or university based. Genes start and end in public domain. Ideally, labs make testing available on fee-for-service basis for 10 years.

4. Methods of Diagnosis For genes in which there is a predominant mutation, that mutation will be screened for first. For most genes, private mutations must be sought using PCR and sequencing exon by exon. For certain genes and mutations, other methodologies may be employed.

5. Examples - Pilot Attempts(~$5000 per gene) Greenwood Genetics Center CDG 1b (phosphomannose isomerase) CDG 1c (hALG6) Gene Dx TNFRSF6 (autoimmune lymphoproliferative syndrome Ia) Emory MUT (methylmalonylCoA mutase)

6. Where are we now? Companies have agreed in principle. Intellectual Property Dept. is running patent searches. If patents are not problematic, we will pursue the four genes mentioned. Next step: Expand within NHGRI. Then: Use this example for other Institutes, perhaps in partnership with NHGRI/ORD.