Early Diagnosis of Werner's Syndrome Using Exome-Wide Sequencing in a Single, Atypical Patient.
Eleanor Raffan, Liam A Hurst, Saeed Al Turki, Gillian Carpenter, Carol Scott, Allan Daly, Alison Coffey, Sanjeev Bhaskar, Eleanor Howard, Naz Khan, Helen Kingston, Aarno Palotie, David B Savage, Mark O'Driscoll, Claire Smith, Stephen O'Rahilly, Inês Barroso, Robert K Semple
Frontiers in Endocrinology | Published : 2011
Genetic diagnosis of inherited metabolic disease is conventionally achieved through syndrome recognition and targeted gene sequencing, but many patients receive no specific diagnosis. Next-generation sequencing allied to capture of expressed sequences from genomic DNA now offers a powerful new diagnostic approach. Barriers to routine diagnostic use include cost, and the complexity of interpreting results arising from simultaneous identification of large numbers of variants. We applied exome-wide sequencing to an individual, 16-year-old daughter of consanguineous parents with a novel syndrome of short stature, severe insulin resistance, ptosis, and microcephaly. Pulldown of expressed sequence..View full abstract