Mutations in the mesenchymal epithelial transition factor (MET) gene are frequently associated with multiple human cancers but can also lead to human non-syndromic autosomal recessive deafness (DFNB97). In the present study, we identified a novel homozygous missense mutation in the METgene causing a non-syndromic hearing impairment DFNB97 form. Whole-exome sequencing was performed to determine the genetic causes of hearing loss in a Moroccan consanguineous family with an affected daughter. The structural analysis of native and mutant in the SEMA domain of the MET receptor was investigated using a molecular dynamics simulation (MDS) approach. We identified a novel pathogenic homozygous c.948A#x3e;G (p.Ile316Met) mutation in the MET gene in one deaf Moroccan young girl carrying a total bilateral non-syndromic hearing impairment. The results of the MDS approach show that an Ile316Met mutation in the SEMA domain leads to protein flexibility loss. This may produce a major impact on the structural conformation of the MET receptor, which also affects the function and binding site of the receptor. This is the first time that a mutation in the MET gene is described in a Moroccan family. Moreover, this study reports the second family in the world associating deafness and mutation in the MET gene.
Hum Hered 2019;84:109–116

中文翻译：

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MET基因在非综合征性常染色体隐性耳聋中的作用的进一步证据

间充质上皮转化因子（MET）基因突变通常与多种人类癌症相关，但也可能导致人类非综合征性常染色体隐性遗传性耳聋（DFNB97）。在本研究中，我们在MET基因中发现了一种新的纯合错义突变，该突变导致非综合征性听力障碍DFNB97形式。进行全外显子测序以确定在摩洛哥近亲家庭中有患病女儿的听力损失的遗传原因。使用分子动力学模拟（MDS）方法研究了MET受体的SEMA域中的天然和突变体的结构分析。我们在MET中鉴定了一种新的致病性纯合c.948A＃x3e; G（p.Ile316Met）突变一名聋哑摩洛哥少女携带双侧非综合征性听力障碍的基因。MDS方法的结果表明，SEMA域中的Ile316Met突变导致​​蛋白质柔韧性损失。这可能对MET受体的结构构象产生重大影响，这也影响该受体的功能和结合位点。这是摩洛哥家庭第一次描述MET基因突变。此外，这项研究报告了世界上第二个与MET基因失聪和突变相关的家族。
嗡嗡声到来的2019; 84：109–116