Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients

Maya Kuperberg, Dorit Lev, Lubov Blumkin, Ayelet Zerem, Mira Ginsberg, Ilan Linder, Nirit Carmi, Sarah Kivity, Tally Lerman-Sagie, Esther Leshinsky-Silver; August 29, 2016, doi: 10.1177/0883073816664836

When a patient arrives with a suspected monogenic disease the authors first take detailed history, perform a full clinical exam, and create a family tree. If a specific genetic disease is suspected based on this data, direct traditional tests are to be performed. Only if the patient remains undiagnosed should the authors turn to whole exome sequencing. The authors were able to diagnose patients exhibiting nonspecific, atypical, or overlapping symptoms.

Over 300 genetic conditions are known to cause ataxia, and without additional specific symptoms achieving a diagnosis is very difficult. Whole exome sequencing studies on cerebellar ataxia have achieved a success rate of 18%-64%. The authors report a high success rate of 57.1% for patients with ataxia.

 Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients