Genetic heterogeneity in GJB2, COL4A3, ATP6V1B1 and EDNRB variants detected among hearing impaired families in Morocco
Genetic heterogeneity in GJB2, COL4A3, ATP6V1B1 and EDNRB variants detected among hearing impaired families in Morocco
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DOI：
10.1007/s11033-022-07245-z
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发表时间：
2022-03-17
影响因子：
2.8
通讯作者：
Barakat, Adbelhamid
中科院分区：
文献类型：
--
作者：
AitRaise, Imane;Amalou, Ghita;Barakat, Adbelhamid
背景耳聋是人类最常见的感觉神经缺陷。它可能是由于外耳道受累、声音传导机制缺陷或耳蜗、耳蜗神经或中枢听觉知觉受损而发生的。遗传原因是最常见的，因为大约70%的听力障碍是遗传性的，分为两组，综合征（与其他症状相关）和非综合征（孤立性耳聋）。方法对6个摩洛哥家系进行全外显子组测序，以确定听力损失的遗传原因，并使用桑格测序验证这些基因的突变。6个家族中有4个家族的研究结果显示，GJB2、COL4A3、ATP 6V1B1和EDNRB基因中存在4种遗传变异，导致非综合征性和综合征性听力损失。多个生物信息学程序和分子建模预测了这些突变的致病作用。结论：我们在摩洛哥耳聋患者中发现了四种纯合突变。这些结果显示了全外显子组测序在鉴定具有多个基因的异质性疾病中的致病性突变方面的重要性。
Background Deafness is the most prevalent human sensorineural defect. It may occur as a result of an external auditory canal involvement, or a deficiency in the sound conduction mechanism, or an impairment of the cochlea, the cochlear nerve or central auditory perception. The genetic causes are the most common, as approximately 70% of hearing disorders are of hereditary origin, divided into two groups, syndromic (associated with other symptoms) and no syndromic (isolated deafness). Methods A whole exome sequencing was performed to identify the genetic cause of hearing loss in six Moroccan families and Sanger sequencing was used to validate mutations in these genes. The results The results of four out of the six families revealed four genetic variants in the genes GJB2, COL4A3, ATP6V1B1 and EDNRB responsible for non-syndromic and syndromic hearing loss. Multiple Bioinformatics programs and molecular modelling predicted the pathogenic effect of these mutations. Conclusions We identified in Moroccan deaf patients four homozygous mutations. These results show the importance of whole exome sequencing to identify pathogenic mutations in heterogeneous disorders with multiple genes responsible.