伴前庭导水管扩大耳聋患儿的致病变异分析与SLC26A4拷贝数变异的回顾性研究OA北大核心CSTPCD

Objective To report unique pathogenic variants in SLC26A4 in a child with deafness and enlarged ves-tibular aqueduct(EVA),as well as copy number variation(CNV)in SLC26A4.Methods Multiplex polymerase chain re-action(PCR)and next-generation sequencing of the coding exons and flanking regions of the SLC26A4 gene were per-formed in the proband and his parents.The sequencing data were analyzed to detect CNV,and breakpoint locations were determined by long-distance PCR amplification and Sanger sequencing.Results The next-generation sequencing of the SLC26A4 gene revealed a c.919-2A>G heterozygous variant in the proband and his father.CNV analysis suggested a large deletion in exons 5 and 6 of the SLC26A4 gene in the proband and his mother.The length of this deletion was de-termined to be 1845bp by long-distance PCR and Sanger sequencing.Alu elements may be involved in generating this deletion by analyzing sequences at both ends of the breakpoint.As of 2024,a total of seven SLC26A4 CNVs have been documented,which are all exonic deletions involving exons 1-8 and 11-18.Conclusion In this study,we identified the genetic etiology of the proband and the precise breakpoint location of the deletion in exons 5 and 6 of the SLC26A4 gene,which is helpful for the genetic diagnosis and counseling for this family.The retrospective analysis of SLC26A4 CNVs indicates that assessing the deletion of exons in the SLC26A4 gene is essential in patients with hearing loss and EVA,particularly in cases where a definitive molecular diagnosis is absent.