Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel

Maggie Brett, John McPherson, Zhi Jiang Zang, Angeline Lai, Ee Shien Tan, Ivy Ng, Lai Choo Ong, Breana Cham, Patrick Tan, Steve Rozen, Ene Choo Tan

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Article numbere93409
JournalPLoS One
Volume9
Issue number4
DOIs
Publication statusPublished - 1 Apr 2014
Externally publishedYes

Fingerprint

High-Throughput Nucleotide Sequencing
Intellectual Disability
Genes
Developmental Disabilities
genes
Phenotype
phenotype
etiology
Neural Cell Adhesion Molecule L1
nonsense mutation
Nonsense Codon
Autistic Disorder
Autism Spectrum Disorder
autism
high-throughput nucleotide sequencing
mutation
Mutation
Testing

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel. / Brett, Maggie; McPherson, John; Zang, Zhi Jiang; Lai, Angeline; Tan, Ee Shien; Ng, Ivy; Ong, Lai Choo; Cham, Breana; Tan, Patrick; Rozen, Steve; Tan, Ene Choo.

In: PLoS One, Vol. 9, No. 4, e93409, 01.04.2014.

Research output: Contribution to journalArticle

Brett, M, McPherson, J, Zang, ZJ, Lai, A, Tan, ES, Ng, I, Ong, LC, Cham, B, Tan, P, Rozen, S & Tan, EC 2014, 'Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel', PLoS One, vol. 9, no. 4, e93409. https://doi.org/10.1371/journal.pone.0093409
Brett, Maggie ; McPherson, John ; Zang, Zhi Jiang ; Lai, Angeline ; Tan, Ee Shien ; Ng, Ivy ; Ong, Lai Choo ; Cham, Breana ; Tan, Patrick ; Rozen, Steve ; Tan, Ene Choo. / Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel. In: PLoS One. 2014 ; Vol. 9, No. 4.
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