Gao Song, Jiang Yi, Wang Guojian, Yuan Yongyi, Huang Shasha, Gao Xue, Li Xiaohong, Zhang Dejun, Wu Jian, Ji Xiaowen, Deng Tao, Wang Ligang, Kang Dongyang, Dai Pu
Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China; Department of Otolaryngology, The 175th Hospital of PLA, South-East Hospital Affiliated to Xiamen University, Zhangzhou, China.
Department of Otolaryngology, Fujian Medical University ShengLi Clinical College, Fujian Provincial Hospital, Fuzhou, China.
Int J Pediatr Otorhinolaryngol. 2018 Oct;113:88-93. doi: 10.1016/j.ijporl.2018.07.022. Epub 2018 Jul 17.
Hereditary nonsyndromic hearing loss is extremely heterogeneous and an X-linked form accounts for 1-5% of all cases. The aim of this study was to identify the pathogenic variants in a nonsyndromic X-linked dominant hearing loss family, and explain the reason of different hearing phenotype in hearing between the two sisters with the same variant.
Targeted gene capture and next-generation sequencing were used to study the genetic cause. What's more, methylation differences among the androgen receptor genes were used to investigate whether the different hearing levels of the two sisters is related to X-chromosome inactivation (Xi).
We identified SMPX c.29insA (p.Asn10Lysfs*3) as the novel variant causing deafness. The skewed X-chromosome inactivation was relevant to the hearing difference between the two sisters.
Targeted gene capture and NGS is an efficient way to identify pathogenic variants in genes. Analysis of X-chromosome inactivation is beneficial to the diagnosis and genetic counseling of X-linked dominant hearing loss families.
遗传性非综合征性听力损失具有高度异质性，其中X连锁型占所有病例的1%-5%。本研究旨在鉴定一个非综合征性X连锁显性听力损失家系中的致病变异，并解释具有相同变异的两姐妹听力表型不同的原因。
采用靶向基因捕获和二代测序研究遗传病因。此外，利用雄激素受体基因的甲基化差异来研究两姐妹不同听力水平是否与X染色体失活（Xi）有关。
我们鉴定出SMPX基因c.29insA（p.Asn10Lysfs*3）为导致耳聋的新变异。X染色体失活偏倚与两姐妹的听力差异有关。
靶向基因捕获和二代测序是鉴定基因致病变异的有效方法。分析X染色体失活有助于X连锁显性听力损失家系的诊断和遗传咨询。
