Novel homozygous ataxia‑telangiectasia (A‑T) mutated gene mutation identified in a Chinese pedigree with A‑T

Chen,Weicheng; Liu,Sida; Hu,Huifang; Chen,Gang; Zhu,Shaicheng; Jia,Bing; Sheng,Wei; Huang,Guoying

doi:10.3892/mmr.2019.10402

Novel homozygous ataxia‑telangiectasia (A‑T) mutated gene mutation identified in a Chinese pedigree with A‑T

Authors:
- Weicheng Chen
- Sida Liu
- Huifang Hu
- Gang Chen
- Shaicheng Zhu
- Bing Jia
- Wei Sheng
- Guoying Huang
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Affiliations: Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102, P.R. China, Department of Pediatric Cardiothoracic Surgery, Maternal and Child Health Hospital of Yancheng, Yancheng, Jiangsu 224002, P.R. China
Published online on: June 20, 2019 https://doi.org/10.3892/mmr.2019.10402
Pages: 1655-1662
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ataxia‑telangiectasia (A‑T) syndrome is a rare autosomal recessive disorder mainly caused by mutations in the A‑T mutated (ATM) gene. However, the genomic abnormalities and their consequences associated with the pathogenesis of A‑T syndrome remain to be fully elucidated. In the present study, a whole‑exome sequencing analysis of a family with A‑T syndrome was performed, revealing a novel homozygous deletion mutation [namely, NM_000051.3:c.50_72+7del,p.Asp18_Lys24delins(23)] in ATM in three affected siblings, which was inherited from their carrier parents who exhibited a normal phenotype in this pedigree. The identified mutation spans the exon 2 and intron 2 regions of the ATM gene, causing a splicing aberration that resulted in a 30‑bp deletion in exon 2 and intron 2, as well as a 71‑bp insertion in intron 2 in the splicing process, which was confirmed by reverse transcription‑polymerase chain reaction and sequencing analysis. The change in the three‑dimensional structure of the protein caused by the mutation in ATM may affect the functions associated with telomere length maintenance and DNA damage repair. Taken together, the present study reported a novel homozygous deletion mutation in the ATM gene resulting in A‑T syndrome in a Chinese pedigree and expanded on the spectrum of known causative mutations of the ATM gene.

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