Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients

Clin Genet. 2018 Mar;93(3):567-576. doi: 10.1111/cge.13102. Epub 2017 Oct 4.

Abstract

Although whole-exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising all OMIM-referenced genes called "medical exome" (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non-syndromic intellectual disability (NSID, n = 33), syndromic ID (NSID = 122), pediatric neurodegenerative disorders (n = 7) and autism spectrum disorder (ASD, n = 54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool.

Keywords: autism; intellectual disability; medical exome; molecular strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Child
  • Child, Preschool
  • Computational Biology / methods
  • Exome Sequencing*
  • Female
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Inheritance Patterns
  • Male
  • Middle Aged
  • Neurodevelopmental Disorders / diagnosis
  • Neurodevelopmental Disorders / genetics*
  • Phenotype
  • Sequence Analysis, DNA / methods
  • Young Adult