Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss.
Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss.
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DOI：
10.1186/s13023-017-0708-z
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发表时间：
2017-09-25
影响因子：
3.7
通讯作者：
Matsunaga T
中科院分区：
文献类型：
--
作者：
Yamamoto N;Mutai H;Namba K;Morita N;Masuda S;Nishi Y;Nakano A;Masuda S;Fujioka M;Kaga K;Ogawa K;Matsunaga T
迄今为止，已有 102 个基因被报道与非综合征性听力损失有关，其中一些与特定的听力图特征相关。据报道，有四种基因可导致中频感音神经性听力损失（MFSNHL），其中 TECTA 是最常报道的；然而，TECTA 突变的发生率尚不清楚。为了阐明 MFSNHL 中 TECTA 突变的患病率并阐明基因型-表型相关性，我们分析了 MFSNHL 患者的遗传和临床特征。对双侧非综合征性听力损失受试者进行 GJB2 和 m.1555A > G 和 m.3243A > G 线粒体 DNA 突变的预筛查，并排除内耳畸形患者。我们选择听力图符合 GENDEAF 研究组提出的 U 形标准的 MFSNHL 患者以及浅 U 形听力图的患者进行 TECTA 分析。所有 TECTA 外显子均通过桑格测序进行分析。根据遗传数据，新的错义变异被分为可能致病的、非致病的和意义不确定的变异。为了评估新的可能致病变异，我们通过分子建模预测了蛋白质结构的变化。在 67 名 MFSNHL 患者中，有 4 名 (6.0%) 发现了 TECTA 的致病性和可能致病性变异。在 U 形听力图的患者中，21 名患者中没有人 (0%) 有致病性或可能致病性变异。在具有浅 U 形听力图的患者中，46 名患者中有 4 名（8.7%）存在致病性或可能致病性变异。鉴定出两种新的可能致病变异，并且先前报告的两种突变被认为是意义未知的变异。致病性和可能致病性变异患者的临床特征与既往研究一致。在具有常染色体显性遗传家族史的 23 个家族中，有 3 个（13.0%）被鉴定出致病性或可能致病性变异；在具有散发性或常染色体隐性遗传家族史的 44 个家族中，有 1 个家族（2.3%）被鉴定出致病或可能致病变异。 6.0% 的 MFSNHL 患者中发现了 TECTA 突变。这些突变在浅U形听力图患者中比在U形听力图患者中更常见，并且在有常染色体显性遗传家族史的家庭中比在散发性或常染色体隐性遗传家族史的家庭中更常见。本文的在线版本 (10.1186/s13023-017-0708-z) 包含补充材料，可供授权用户使用。
To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL. Subjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling. Pathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive. TECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive. The online version of this article (10.1186/s13023-017-0708-z) contains supplementary material, which is available to authorized users.
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64.8
作者：
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