Novel TECTA Mutations Identified in Stable Sensorineural Hearing Loss and Their Clinical Implications
Novel TECTA Mutations Identified in Stable Sensorineural Hearing Loss and Their Clinical Implications
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DOI：
10.1159/000366514
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发表时间：
2015-01-01
影响因子：
1.6
通讯作者：
Choi, Byung Yoon
中科院分区：
文献类型：
--
作者：
Kim, Ah Reum;Chang, Mun Young;Choi, Byung Yoon
TECTA是常染色体显性遗传（DFNA 8/A12）和常染色体隐性遗传（DFNB 21）的非综合征型感音神经性耳聋（NSHL）的致病基因。TECTA突变占某些人群中所有常染色体显性NSHL病例的4%，因此被认为是常染色体显性NSHL的主要原因之一。已提出TECTA基因中常染色体显性突变的基因型-表型相关性。两个家庭（SB 146和SB 149），分离中度NSHL的常染色体显性遗传的方式，包括在这项研究中。我们对134个已知的耳聋基因（TRS-134）进行了靶向重测序和生物信息学分析，以发现这两个家族中NSHL的致病突变。通过TRS-134检测，我们在TECTA基因中发现了2个新的突变，即c.3995G>T（p.C1332F）和c.5618C>T（p.T1873I）。这些突变共分离与NSHL在研究的家庭，并没有检测到正常对照。突变c.3995G>T和c.5618C>T分别位于带状粘附素（ZA）结构域和透明带（ZP）结构域的血管性血友病因子D3-D4型（vWFD 3-D4）结构域间。p.C1332F是在ZA结构域的vWFD 3-D4结构域间检测到的第一个突变。突变p.C1332F和p.T1873I分别与稳定的高频和中频听力损失相关。值得注意的是，SB 146中突变为苯丙氨酸的半胱氨酸残基与感音神经性听力损失的进展无关，这与先前的假设相反。在这里，我们确认了已知的基因型-表型相关性的ZP域，并提出了一个假设的基因型-表型相关性vWFD 3-D4的突变，稳定的高频NSHL在韩国人。这种临床特征使得TECTA的vWFD 3-D4结构域中具有错义突变的受试者成为中耳植入的潜在良好候选者。(c)2014 S. Karger AG，巴塞尔
TECTA is a causative gene of autosomal dominant (DFNA8/A12) and autosomal recessive (DFNB 21) nonsyndromic sensorineural hearing loss (NSHL). Mutations in TECTA account for 4% of all autosomal dominant NSHL cases in some populations and are thus thought to be one of the major causes of autosomal dominant NSHL. A genotype-phenotype correlation for autosomal dominant mutations in the TECTA gene has been proposed. Two families (SB146 and SB149), which segregated moderate NSHL in an autosomal dominant fashion, were included in this study. We performed targeted resequencing of 134 known deafness genes (TRS-134) and bioinformatics analyses to find causative mutations for NSHL in these 2 families. Through TRS-134, we detected 2 novel mutations, i.e. c.3995G>T (p.C1332F) and c.5618C>T (p.T1873I), in the TECTA gene. These mutations cosegregated with NSHL in the studied families and were not detected in normal controls. The mutations c.3995G>T and c.5618C>T reside in the von Willebrand factor type D3-D4 (vWFD3-D4) interdomain of the zonadhesin (ZA) domain and the zona pellucida (ZP) domain, respectively. p.C1332F is the first mutation detected in the vWFD3-D4 interdomain of the ZA domain. The mutations p.C1332F and p.T1873I were associated with stable high-frequency and mid-frequency hearing loss, respectively. Notably, the cysteine residue mutated to phenylalanine in SB146 was not related to progression of sensorineural hearing loss, which argues against the previous hypothesis. Here we confirm a known genotype-phenotype correlation for the ZP domain and propose a hypothetical genotype-phenotype correlation which relates mutations in vWFD3-D4 to stable high-frequency NSHL in Koreans. This clinical feature makes subjects with the missense mutation in the vWFD3-D4 interdomain of TECTA potentially good candidates for middle ear implantation. (c) 2014 S. Karger AG, Basel