A guide for the diagnosis of rare and undiagnosed disease: beyond the exome

Rare diseases affect 30 million people in the USA and more than 300-400 million worldwide, often causing chronic illness, disability, and premature death. Traditional diagnostic techniques rely heavily on heuristic approaches, coupling clinical experience from prior rare disease presentations with the medical literature. A large number of rare disease patients remain undiagnosed for years and many even die without an accurate diagnosis. In recent years, gene panels, microarrays, and exome sequencing have helped to identify the molecular cause of such rare and undiagnosed diseases. These technologies have allowed diagnoses for a sizable proportion (25-35%) of undiagnosed patients, often with actionable…

• NI
  National Institutes of Health

  Awards: U41HG009649, U01HG010218, U41HG009649, R01DK116750, R01DK120565, P30DK116074, P30DK116074, R01 DK116750, R01 DK120565
• CF
  Common Fund

  Award: U01HG010218