Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Am J Med Genet A. 2013 Sep;161A(9):2226-33. doi: 10.1002/ajmg.a.36068. Epub 2013 Aug 5.
Recessive mutations in SLC26A4 and in rarer cases double heterozygous mutations of FOXI1/SLC26A4 and KCNJ10/SLC26A4 lead to hearing impairment associated with enlarged vestibular aqueduct (EVA), the most common inner ear malformation. In our large cohort study, we addressed several important questions to the molecular etiology of this disorder. The overall prevalence of SLC26A4 mutations in nonsyndromic childhood sensorineural hearing loss (11.2%, 37/330) were determined by sequencing of SLC26A4 in 330 hearing impaired children who did not undergo inner ear radiologic imaging prior to their genetic test. The penetrance of EVA in bi-allelic SLC26A4 mutation carriers (100%, 37/37) was determined by follow-up computed tomography scanning. Combined with the study of 140 additional probands diagnosed with nonsyndromic EVA, we characterized the mutation spectrum of SLC26A4 in East China, which consisted of 19 novel SLC26A4 mutations and differed from those reported in other regions of China.
SLC26A4 中的隐性突变，以及更罕见的 FOXI1/SLC26A4 和 KCNJ10/SLC26A4 双重杂合突变，导致与扩大的前庭水管（EVA）相关的听力损失，这是最常见的内耳畸形。在我们的大型队列研究中，我们针对这种疾病的分子病因学提出了几个重要问题。通过对 330 名听力受损儿童进行 SLC26A4 测序，确定了未进行内耳影像学检查的非综合征性儿童感音神经性听力损失（11.2%，37/330）中 SLC26A4 突变的总体患病率。通过后续的计算机断层扫描确定双等位基因 SLC26A4 突变携带者中 EVA 的外显率（100%，37/37）。结合对另外 140 名被诊断为非综合征性 EVA 的先证者的研究，我们描述了华东地区 SLC26A4 的突变谱，其中包括 19 个新的 SLC26A4 突变，与中国其他地区报道的突变不同。
