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)

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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.