LHFPL5 mutation: A rare cause of non-syndromic autosomal recessive hearing loss
LHFPL5 mutation: A rare cause of non-syndromic autosomal recessive hearing loss
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DOI：
10.1016/j.ejmg.2018.11.026
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发表时间：
2019-12-01
影响因子：
1.9
通讯作者：
Ali, Manir
中科院分区：
文献类型：
--
作者：
Al-Amri, Ahmed H.;Al Saegh, Abeer;Ali, Manir
听力损失是一种使人衰弱的疾病，会损害语言习得，导致儿童残疾和成年后的潜在孤立。它的发病可能有遗传基础，尽管通常可以预防的环境因素也可能导致这种情况。遗传形式是高度异质性的，早期发现是必要的，以安排适当的病人支持。在这里，我们报告了遗传性听力损失的分子基础，在一个近亲家庭与多个受影响的成员从阿曼。将纯合性作图与全外显子组测序相结合，在脂肪瘤HMGIC融合伴侣样5基因（LHFPL 5）中鉴定出一种新的纯合性核苷酸替换c.575T > C，其将蛋白质中的第192个氨基酸残基从亮氨酸转化为脯氨酸，p.（Leu192Pro）。桑格测序证实了与隐性疾病预期的疾病表型分离，并且在来自各种疾病特异性和群体遗传研究的123，490名受试者以及150名无关个体和35名阿曼族耳聋患者中不存在该变体。这项研究描述了一个具有遗传性听力损失的阿曼血统家庭中的一种新型LHFPL 5突变，支持了以前对这种情况的临床描述，并有助于这种形式的耳聋突变的遗传谱。
Hearing loss is a debilitating disorder that impairs language acquisition, resulting in disability in children and potential isolation in adulthood. Its onset can have a genetic basis, though environmental factors, which are often preventable, can also cause the condition. The genetic forms are highly heterogeneous, and early detection is necessary to arrange appropriate patient support. Here we report the molecular basis of hereditary hearing loss in a consanguineous family with multiple affected members from Oman. Combining homozygosity mapping with whole exome sequencing identified a novel homozygous nucleotide substitution c.575T > C in the lipoma HMGIC fusion partner-like 5 gene (LHFPL5), that converted the 192nd amino acid residue in the protein from a leucine to a proline, p.(Leu192Pro). Sanger sequencing confirmed segregation with the disease phenotype as expected for a recessive condition and the variant was absent in 123,490 subjects from various disease-specific and population genetic studies as well as 150 unrelated individuals and 35 deaf patients of Omani ethnicity. This study, which describes a novel LHFPL5 mutation in a family of Omani origin with hereditary hearing loss, supports previous clinical descriptions of the condition and contributes to the genetic spectrum of mutations in this form of deafness.