A dominant variant in DMXL2 is linked to nonsyndromic hearing loss
A dominant variant in DMXL2 is linked to nonsyndromic hearing loss
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DMXL2 的显性变异与非综合征性听力损失有关
DOI：
10.1038/gim.2016.142
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发表时间：
2017-05-01
影响因子：
8.8
通讯作者：
Wu, Hao
中科院分区：
文献类型：
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作者：
Chen, Dong-Ye;Liu, Xing-Feng;Wu, Hao
目的：探讨一个以晚发型、进行性、非综合征性耳聋为主的家系中耳聋的遗传病因。通过对选定的家系成员进行全外显子测序，确定了候选致病变异体，并对所有家系成员进行了Sanger测序。结果：Dmxl2基因定位于染色体15q21上的9.68-Mb候选区域。2(优势分数的最大对数=4.03)，不包含先前描述的耳聋基因。全外显子测序证实DMXL2中的杂合子c.7250G>；A(p.Arg2417His)是分离听力损失的唯一候选致病变异体。结论：DMXL2基因2417His变异与遗传性、非综合征性听力损失有关，提示DMXL2在内耳功能中起重要作用。
Purpose:To explore the genetic etiology of deafness in a dominant family with late-onset, progressive, nonsyndromic hearing loss.Methods:Genome-wide linkage analysis was performed for 21 family members. Candidate pathogenic variants were identified by whole-exome sequencing of selected family members and confirmed by Sanger sequencing of all family members. Cochlear expression of Dmxl2 was investigated by reverse-transcription polymerase chain reaction (RT-PCR) and immunostaining of the organ of Corti from mice.Results:The causative gene was mapped to a 9.68-Mb candidate region on chromosome 15q21. 2 (maximum logarithm of the odds score= 4.03) that contained no previously described deafness genes. Whole-exome sequencing identified heterozygous c. 7250G> A (p. Arg2417His) in DMXL2 as the only candidate pathogenic variant segregating the hearing loss. In mouse cochlea, expression of DMXL2 was restricted to the hair cells and the spiral ganglion neurons.Conclusion:Our data indicated that the p. Arg2417His variant in DMXL2 is associated with dominant, nonsyndromic hearing loss and suggested an important role of DMXL2 in inner ear function.