Affiliations 

  • 1 KK Research Centre, KK Women's & Children's Hospital, Singapore, Singapore
  • 2 Duke-NUS Graduate Medical School, Singapore, Singapore
  • 3 National Cancer Centre, Singapore, Singapore
  • 4 Genetic Services, KK Women's & Children's Hospital, Singapore, Singapore
  • 5 Universiti Malaya Medical Centre, Petaling Jaya, Malaysia
  • 6 Duke-NUS Graduate Medical School, Singapore, Singapore; National Cancer Centre, Singapore, Singapore
PLoS One, 2014;9(4):e93409.
PMID: 24690944 DOI: 10.1371/journal.pone.0093409

Abstract

Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81-84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.