Diagnosing rare diseases can be prolonged and costly, both in emotional distress for families and in medical expenditures. Although not all rare conditions are heritable, a substantial number result from mutations with large effect in one or a few genes. The genetic bases for approximately 40% of the over 7000 suspected Mendelian disorders are now known, though clinical testing is not available for all.62 For conditions with known or suspected causal variants, advances in genotyping and sequencing targeted genomic regions have led to increasingly routine use of these technologies as diagnostic aids. Conversely, the fact that approximately 60% of the suspected 7000 Mendelian disorders lack a known basis leaves significant room for discovery.
