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

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.