A Dominant Mutation in the Stereocilia-Expressing Gene TBC1D24 is a Probable Cause for Nonsyndromic Hearing Impairment
A Dominant Mutation in the Stereocilia-Expressing Gene TBC1D24 is a Probable Cause for Nonsyndromic Hearing Impairment
复制标题
立体纤毛表达基因 TBC1D24 的显性突变是非综合征性听力障碍的可能原因
DOI：
10.1002/humu.22558
复制
发表时间：
2014-07-01
期刊：
影响因子：
3.9
通讯作者：
Wu, Hao
中科院分区：
文献类型：
--
作者：
Zhang, Luping;Hu, Lingxiang;Wu, Hao
TBC1D24突变与多种癫痫综合征有关，最近与综合征性听力损伤DOORS综合征和非综合征性听力损伤DFNB 86有关。迄今为止报道的所有TBC1D24突变均以隐性模式遗传。在一个晚发型、进行性、非综合征性听力障碍的显性家系中，连锁分析显示染色体16p13.3上有一个2.07Mb的候选区域，包含TBC1D24。全外显子组测序鉴定了TBC1D24的一个杂合p.Ser178Leu变异体作为该家族中与听力损失分离的唯一候选突变。在围产期小鼠耳蜗，我们检测到Tbc1d24的限制性表达的静纤毛的毛细胞，以及在螺旋神经节神经元。我们的研究表明，TBC1D24的p.Ser178Leu突变可能是显性的，非综合征性听力障碍的原因。TBC1D24作为静纤毛表达基因的鉴定可能为其在内耳中的特定功能提供新的线索。
Mutations in TBC1D24 have been linked to a variety of epileptic syndromes and recently to syndromic hearing impairment DOORS syndrome and nonsyndromic hearing impairment DFNB86. All TBC1D24 mutations reported so far were inherited in the recessive mode. In a dominant family segregated with late-onset, progressive, nonsyndromic hearing impairment, linkage analysis revealed a 2.07Mb candidate region on chromosome 16p13.3 that contains TBC1D24. Whole-exome sequencing identified a heterozygous p.Ser178Leu variant of TBC1D24 as the only candidate mutation segregating with the hearing loss within the family. In perinatal mouse cochlea, we detected a restricted expression of Tbc1d24 in the stereocilia of the hair cells as well as in the spiral ganglion neurons. Our study suggested that the p.Ser178Leu mutation of TBC1D24 is a probable cause for dominant, nonsyndromic hearing impairment. Identification of TBC1D24 as the stereocilia-expressing gene may shed new light on its specific function in the inner ear.