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

Publication ,  Journal Article
Brett, M; McPherson, J; Zang, ZJ; Lai, A; Tan, E-S; Ng, I; Ong, L-C; Cham, B; Tan, P; Rozen, S; Tan, E-C
Published in: PLoS One
2014

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

4

Start / End Page

e93409

Location

United States

Related Subject Headings

  • RNA Splice Sites
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Mutation
  • Male
  • Intellectual Disability
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Genome-Wide Association Study
  • Genetic Variation
 

Citation

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Brett, M., McPherson, J., Zang, Z. J., Lai, A., Tan, E.-S., Ng, I., … Tan, E.-C. (2014). Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel. PLoS One, 9(4), e93409. https://doi.org/10.1371/journal.pone.0093409
Brett, Maggie, John McPherson, Zhi Jiang Zang, Angeline Lai, Ee-Shien Tan, Ivy Ng, Lai-Choo Ong, et al. “Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel.PLoS One 9, no. 4 (2014): e93409. https://doi.org/10.1371/journal.pone.0093409.
Brett, Maggie, et al. “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, 2014, p. e93409. Pubmed, doi:10.1371/journal.pone.0093409.
Brett M, McPherson J, Zang ZJ, Lai A, Tan E-S, Ng I, Ong L-C, Cham B, Tan P, Rozen S, Tan E-C. Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel. PLoS One. 2014;9(4):e93409.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

4

Start / End Page

e93409

Location

United States

Related Subject Headings

  • RNA Splice Sites
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Mutation
  • Male
  • Intellectual Disability
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Genome-Wide Association Study
  • Genetic Variation