The diagnostic utility of exome sequencing in Joubert syndrome and related disorders

J Hum Genet. 2013 Feb;58(2):113-5. doi: 10.1038/jhg.2012.117. Epub 2012 Oct 4.

Abstract

Joubert syndrome (JS) and related disorders (JSRD) are autosomal recessive and X-linked disorders characterized by hypoplasia of the cerebellar vermis with a characteristic 'molar tooth sign' on brain imaging and accompanying neurological symptoms including episodic hyperpnoea, abnormal eye movements, ataxia and intellectual disability. JSRD are clinically and genetically heterogeneous, and, to date, a total of 17 causative genes are known. We applied whole-exome sequencing (WES) to five JSRD families and found mutations in all: either CEP290, TMEM67 or INPP5E was mutated. Compared with conventional Sanger sequencing, WES appears to be advantageous with regard to speed and cost, supporting its potential utility in molecular diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple
  • Cerebellar Diseases / diagnosis*
  • Cerebellar Diseases / genetics
  • Cerebellum / abnormalities
  • Exome*
  • Eye Abnormalities / diagnosis*
  • Eye Abnormalities / genetics
  • Female
  • Humans
  • Kidney Diseases, Cystic / diagnosis*
  • Kidney Diseases, Cystic / genetics
  • Magnetic Resonance Imaging
  • Male
  • Pedigree
  • Retina / abnormalities
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA*

Supplementary concepts

  • Agenesis of Cerebellar Vermis