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Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole‐exome sequencing
Author(s) -
Hiraide Takuya,
Yamoto Kaori,
Masunaga Yohei,
Asahina Miki,
Endoh Yusaku,
Ohkubo Yumiko,
Matsubayashi Tomoko,
Tsurui Satoshi,
Yamada Hidetaka,
Yanagi Kumiko,
Nakashima Mitsuko,
Hirano Kouichi,
Sugimura Haruhiko,
Fukuda Tokiko,
Ogata Tsutomu,
Saitsu Hirotomo
Publication year - 2021
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13951
Subject(s) - exome sequencing , intellectual disability , phenotype , genetics , exome , biology , global developmental delay , computational biology , medicine , bioinformatics , evolutionary biology , gene
Whole‐exome sequencing (WES) enables identification of pathogenic variants, including copy number variants (CNVs). In this study, we performed WES in 101 Japanese patients with unexplained developmental delay (DD) or intellectual disability (ID) (63 males and 38 females), 98 of them with trio‐WES. Pathogenic variants were identified in 54 cases (53.5%), including four cases with pathogenic CNVs. In one case, a pathogenic variant was identified by reanalysis of exome data; and in two cases, two molecular diagnoses were identified. Among 58 pathogenic variants, 49 variants occurred de novo in 48 patients, including two somatic variants. The accompanying autism spectrum disorder and external ear anomalies were associated with detection of pathogenic variants with odds ratios of 11.88 (95% confidence interval [CI] 2.52–56.00) and 3.46 (95% CI 1.23–9.73), respectively. These findings revealed the importance of reanalysis of WES data and detection of CNVs and somatic variants in increasing the diagnostic yield for unexplained DD/ID. In addition, genetic testing is recommended when patients suffer from the autism spectrum disorder or external ear anomalies, which potentially suggests the involvement of genetic factors associated with gene expression regulation.