后天性非综合征型听力损失表型：一例 MYO15A 和 MITF 中存在 2 个双等位基因突变的多基因病例。
Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF.
机构信息
Departments of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Otolaryngology - Head and Neck Surgery, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
出版信息
BMC Med Genet. 2020 Jan 2;21(1):1. doi: 10.1186/s12881-019-0942-4.
BACKGROUND
Hearing loss (HL) represents the most common congenital sensory impairment with an incidence of 1-5 per 1000 live births. Non-syndromic hearing loss (NSHL) is an isolated finding that is not part of any other disorder accounting for 70% of all genetic hearing loss cases.
METHODS
In the current study, we reported a polygenic mode of inheritance in an NSHL consanguineous family using exome sequencing technology and we evaluated the possible effect of the detected single nucleotide variants (SNVs) using in silico methods.
RESULTS
Two bi-allelic SNVs were detected in the affected patients; a MYO15A (. p.V485A) variant, and a novel MITF (p.P338L) variant. Along with these homozygous mutations, we detected two heterozygous variants in well described hearing loss genes (MYO7A and MYH14). The novel MITF p. Pro338Leu missense mutation was predicted to change the protein structure and function.
CONCLUSION
A novel MITF mutation along with a previously described MYO15A mutation segregate with an autosomal recessive non-syndromic HL case with a post-lingual onset. The findings highlight the importance of carrying whole exome sequencing for a comprehensive assessment of HL genetic heterogeneity.
背景
听力损失（HL）是最常见的先天性感觉障碍，发病率为每 1000 例活产儿中有 1-5 例。非综合征性听力损失（NSHL）是一种孤立的发现，不属于任何其他疾病，占所有遗传性听力损失病例的 70%。
方法
在本研究中，我们使用外显子组测序技术报告了一个 NSHL 近亲家族的多基因遗传模式，并使用计算机方法评估了检测到的单核苷酸变异（SNVs）的可能影响。
结果
在受影响的患者中检测到两个双等位基因 SNV；一个 MYO15A（. p.V485A）变体和一个新的 MITF（p.P338L）变体。除了这些纯合突变，我们还在两个描述良好的听力损失基因（MYO7A 和 MYH14）中检测到两个杂合变体。新的 MITF p. Pro338Leu 错义突变被预测会改变蛋白质结构和功能。
结论
一个新的 MITF 突变与以前描述的 MYO15A 突变一起，与一种常染色体隐性非综合征性 HL 病例伴后天性发病有关。这些发现强调了对 HL 遗传异质性进行全面评估时进行全外显子组测序的重要性。
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