Aerospace Balance Medical Center, Chinese PLA Air Forch General Hospital, Beijing, China.
Department of Otolaryngology, Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
Acta Otolaryngol. 2022 May;142(5):448-453. doi: 10.1080/00016489.2019.1597984. Epub 2022 May 31.
To date, seven mutations have been reported in families with autosomal dominant non-syndromic hearing loss worldwide. All the mutations cause exon 8 skipping at the mRNA level, that led to the protein truncated and the protein could exert a gain of ototoxic function.
In this study, we found an autosomal-dominant non-syndromic hearing loss Chinese pedigree which spanned four generations and comprised 43 members. We want to identify the causative gene and mutation.
Application of microsatellite markers on DFNA 23 loci preliminary screening of 25 genes, data were analyzed by linkage analysis.
We mapped the locus to the region between D7S629 and D7S516 (two-point lod-score of 5.39) with the application of 8 microsatellite markers. By direct sequencing of candidate genes in mapping region, we identified a novel missense mutation ivs7-2 A > G in DFNA5 gene, which was faithfully cosegregated with hearing loss in the family.
The missense mutation in intron 7 of causes skipping of exon 8, resulting in premature termination of the open reading frame. This type of mutation has repeatedly confirmed that it provides more evidence for the previous view and provides a more solid foundation for future research.
迄今为止，全球范围内已在常染色体显性遗传性非综合征型耳聋的家族中报道了七种突变。所有的突变均导致 mRNA 水平的外显子 8 跳跃，从而导致蛋白截断，蛋白可能发挥耳毒性功能增益。
本研究发现了一个跨越四代、包含 43 名成员的常染色体显性遗传性非综合征型耳聋中国家系。我们希望确定致病基因和突变。
应用微卫星标记对 DFNA23 个基因座进行初步筛选，通过连锁分析对数据进行分析。
我们将该基因座定位在 D7S629 和 D7S516 之间的区域（两点连锁分析的最大 lod 得分为 5.39）。通过对候选基因在该区域的直接测序，我们在 DFNA5 基因中发现了一个新的错义突变 ivs7-2 A > G，该突变在家系中与耳聋完全共分离。
该错义突变位于内含子 7 中，导致外显子 8 跳跃，从而导致开放阅读框提前终止。这种类型的突变已反复证实，为先前的观点提供了更多证据，并为未来的研究提供了更坚实的基础。
