title: Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients.
abstract: Whole exome sequencing enables scanning a large number of genes for relatively low costs. The authors investigate its use for previously undiagnosed pediatric neurological patients. This retrospective cohort study performed whole exome sequencing on 57 patients of "Magen" neurogenetic clinics, with unknown diagnoses despite previous workup. The authors report on clinical features, causative genes, and treatment modifications and provide an analysis of whole exome sequencing utility per primary clinical feature. A causative gene was identified in 49.1% of patients, of which 17 had an autosomal dominant mutation, 9 autosomal recessive, and 2 X-linked. The highest rate of positive diagnosis was found for patients with developmental delay, ataxia, or suspected neuromuscular disease. Whole exome sequencing warranted a definitive change of treatment for 5 patients. Genetic databases were updated accordingly. In conclusion, whole exome sequencing is useful in obtaining a high detection rate for previously undiagnosed disorders. Use of this technique could affect diagnosis, treatment, and prognostics for both patients and relatives.
authors: Metabolic-Neurogenetic Service, Wolfson Medical Center, Holon, Israel maya.kuperberg@gmail.com.
authors: Maya
authors: M
authors: Kuperberg
authors: Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel.
authors: Dorit
authors: D
authors: Lev
authors: Metabolic-Neurogenetic Service, Wolfson Medical Center, Holon, Israel.
authors: Lubov
authors: L
authors: Blumkin
authors: Department of Pediatric Neurology, Wolfson Medical Center, Holon, Israel.
authors: Ayelet
authors: A
authors: Zerem
authors: Department of Pediatric Neurology, Wolfson Medical Center, Holon, Israel.
authors: Mira
authors: M
authors: Ginsberg
authors: Department of Pediatric Neurology, Wolfson Medical Center, Holon, Israel.
authors: Ilan
authors: I
authors: Linder
authors: Department of Pediatric Neurology, Wolfson Medical Center, Holon, Israel.
authors: Nirit
authors: N
authors: Carmi
authors: Department of Pediatric Neurology, Wolfson Medical Center, Holon, Israel.
authors: Sarah
authors: S
authors: Kivity
authors: Metabolic-Neurogenetic Service, Wolfson Medical Center, Holon, Israel.
authors: Tally
authors: T
authors: Lerman-Sagie
authors: Molecular Genetics laboratory, Wolfson Medical Center, Holon, Israel.
authors: Esther
authors: E
authors: Leshinsky-Silver
mesh_terms: D002648:Child; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000235:genetics*; D012189:Retrospective Studies; D000073359:Exome Sequencing
keywords: ataxia; developmental delay; exomics; genetics; neurology