Pediatrics Department, Tawam Hospital, Al Ain, United Arab Emirates.
Genetic Division, Pediatrics Department, Tawam Hospital, Al Ain, United Arab Emirates.
Mol Genet Genomic Med. 2022 Nov;10(11):e2052. doi: 10.1002/mgg3.2052. Epub 2022 Sep 2.
Hearing loss (HL) is a heterogeneous condition that causes partial or complete hearing impairment. Hundreds of variants in >60 genes have been reported to be associated with Hereditary HL (HHL), variants of the GJB2 gene are the most common cause of congenital SNHL, with >100 variants reported. The HHL prevalence is thought to be high in the Arab population; however, the genetic epidemiology of HHL among Emirati populations is understudied.
To shed light on the mutational spectrum of NSHL in Emirati patients seen in the genetic clinic over 10 years and to capture founder mutation(s) if any were identified.
Retrospective chart review of all Emirati patients assessed by clinical geneticists due to NSHL during the period between January 2010 to December 2020. Genetic tests were done based on clinical phenotypes of the patient and family history including targeted mutation testing, next-generation sequencing, or whole-exome sequencing (solo or trio). The authors did literature reviews using PubMed for all previously reported articles related to NSHL genes from UAE.
A total of 162 patients with HL, were evaluated during the period between January 2010 to December 2020. There were 82 patients with NSHL, and only 72 patients who completed the genetic evaluations were included in this retrospective study. Among the studied group, 42 (51.2%) were males and 40 (48.78%) were females. The youngest patient was 2 years old and the oldest patient was 50 years old. Consanguinity was documented in 76 patients (92.68%). A total of 14 mutations reported here are novel (23/72 i.e., 31.9%). Twelve missense mutations, 6 nonsense mutations, 6 frameshift mutations, 2 in-frame deletion mutations, and 1 splice site mutation was found. Variants in the GJB2 gene are the most commonly identified cause of NSHL, with c.35delG being the most followed by c.506G > A. The second commonly found variant is c.934C > G (p.Arg312Gly) in the CDC14A gene, found in 9 patients. This was followed by variants in OTOF and SLC26A4 genes, found in 8 patients, respectively. Chromosomal microdeletions encompassing genes causing NSHL were found in 3 patients. No mitochondrial mutations were found in this study group. A total of 11 previous reports about Emirati patients with NSHL were reviewed, with a total of 35 patients.
Emirati patients with NSHL have several mutations, most notably missense mutations. Novel mutations are worth further testing and represent the area for future researches.
听力损失（HL）是一种引起部分或完全听力障碍的异质性疾病。已有数百种变体在 >60 种基因中被报道与遗传性 HL（HHL）相关，GJB2 基因的变体是先天性 SNHL 的最常见原因，已有 >100 种变体被报道。据认为，阿拉伯人群中的 HHL 患病率很高；然而，阿联酋人群中 HHL 的遗传流行病学研究还很不足。
阐明在过去 10 年中在遗传诊所中看到的阿联酋患者的非综合征性听力损失（NSHL）的突变谱，并捕捉任何已确定的创始人突变。
对 2010 年 1 月至 2020 年 12 月期间因 NSHL 而接受临床遗传学家评估的所有阿联酋患者的病历进行回顾性分析。根据患者的临床表型和家族史进行遗传检测，包括靶向突变检测、下一代测序或外显子组测序（单独或 trio）。作者使用 PubMed 对与阿联酋的 NSHL 基因相关的所有先前发表的文章进行了文献综述。
在 2010 年 1 月至 2020 年 12 月期间，共有 162 名 HL 患者接受了评估。其中有 82 名患者患有 NSHL，只有 72 名完成了遗传评估的患者被纳入本回顾性研究。在所研究的组中，有 42 名（51.2%）为男性，40 名（48.78%）为女性。最年轻的患者为 2 岁，最年长的患者为 50 岁。在 76 名患者（92.68%）中记录了近亲结婚。共报告了 14 种新的突变（23/72，即 31.9%）。发现了 12 种错义突变、6 种无义突变、6 种移码突变、2 种框内缺失突变和 1 种剪接位点突变。GJB2 基因中的变体是最常见的 NSHL 致病原因，c.35delG 是最常见的，其次是 c.506G > A。第二个最常见的变体是 CDC14A 基因中的 c.934C > G（p.Arg312Gly），在 9 名患者中发现。其次是 OTOF 和 SLC26A4 基因中的变体，分别在 8 名患者中发现。在 3 名患者中发现了包含导致 NSHL 的基因的染色体微缺失。在本研究组中未发现线粒体突变。共回顾了 11 篇关于阿联酋 NSHL 患者的先前报告，共 35 名患者。
阿联酋 NSHL 患者有多种突变，最常见的是错义突变。新的突变值得进一步检测，代表了未来研究的方向。
