Department of Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen, China.
Department of Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
Neural Plast. 2021 Apr 22;2021:5528434. doi: 10.1155/2021/5528434. eCollection 2021.
Approximately 70% of congenital deafness is attributable to genetic causes. Incidence of congenital deafness is known to be higher in families with consanguineous marriage. In this study, we investigated the genetic causes in three consanguineous Pakistani families segregating with prelingual, severe-to-profound deafness.
Through targeted next-generation sequencing of 414 genes known to be associated with deafness, homozygous variants c.536del (p. Leu180Serfs∗20) in , c.3719 G>A (p. Arg1240Gln) in , and c.482+1986_1988del in were identified as the pathogenic causes of enrolled families. Interestingly, in one large consanguineous family, an additional c.706G>A (p. Glu236Lys) variant in the X-linked gene was also identified in multiple affected family members causing deafness. Genotype-phenotype cosegregation was confirmed in all participating family members by Sanger sequencing.
Our results showed that the genetic causes of deafness are highly heterogeneous. Even within a single family, the affected members with apparently indistinguishable clinical phenotypes may have different pathogenic variants.
大约 70%的先天性耳聋是由遗传原因引起的。已知近亲结婚家庭的先天性耳聋发病率较高。在这项研究中，我们调查了三个巴基斯坦近亲结婚家庭的遗传原因，这些家庭存在先天性、重度至极重度耳聋的遗传。
通过对已知与耳聋相关的 414 个基因的靶向下一代测序，在 中发现了纯合变体 c.536del（p.Leu180Serfs∗20），在 中发现了 c.3719 G>A（p.Arg1240Gln），在 中发现了 c.482+1986_1988del ，这些都是所纳入家庭的致病原因。有趣的是，在一个大型近亲结婚家庭中，X 连锁的 基因中的 c.706G>A（p.Glu236Lys）变体也在多个受影响的家族成员中被发现，导致耳聋。通过 Sanger 测序在所有参与的家族成员中证实了基因型-表型共分离。
我们的研究结果表明，耳聋的遗传原因高度异质性。即使在单个家庭中，具有明显相似临床表型的受影响成员也可能具有不同的致病变体。
