Abstract：
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.
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.
摘要：
听力损失(HL)是导致部分或完全听力损害的异质性病症。已报道>60个基因中的数百个变异与遗传性HL（HHL）相关，GJB2基因的变异是先天性SNHL的最常见原因，报告>100个变体。人们认为阿拉伯人口中HHL的患病率很高；然而，阿联酋人群中HHL的遗传流行病学研究不足。
阐明在10年以上的遗传诊所中看到的阿联酋患者中NSHL的突变谱，并捕获创始人突变（如果有的话）。
2010年1月至2020年12月期间，由临床遗传学家评估的所有因NSHL引起的阿联酋患者的回顾性图表回顾。根据患者的临床表型和家族史进行基因检测，包括靶向突变检测。下一代测序，或全外显子组测序（独奏或三重奏）。作者使用PubMed对所有先前报道的与UAE的NSHL基因相关的文章进行了文献综述。
共有162例HL患者，在2010年1月至2020年12月期间进行了评估。有82例NSHL患者，本回顾性研究仅包括72例完成基因评估的患者.在研究组中，男性42人（51.2%），女性40人（48.78%）。年龄最小的患者为2岁，年龄最大的患者为50岁。76例患者（92.68％）有血缘关系。这里报道的总共14个突变是新的(23/72即，31.9%）。十二个错义突变，6个无意义的突变，6移码突变，2个框内缺失突变，发现1个剪接位点突变。GJB2基因的变异是NSHL最常见的病因，c.35delG是最多的，其次是c.506G>A。第二个常见的变体是c.934C>G（p。Arg312Gly）在CDC14A基因中，在9名患者中发现。其次是OTOF和SLC26A4基因的变异，在8名患者中发现，分别。在3例患者中发现了包含引起NSHL的基因的染色体微缺失。在该研究组中未发现线粒体突变。回顾了以前关于阿联酋NSHL患者的11份报告，共35名患者。
阿联酋NSHL患者有几种突变，最值得注意的是错义突变。新的突变值得进一步测试，代表了未来研究的领域。
阐明在10年以上的遗传诊所中看到的阿联酋患者中NSHL的突变谱，并捕获创始人突变（如果有的话）。
2010年1月至2020年12月期间，由临床遗传学家评估的所有因NSHL引起的阿联酋患者的回顾性图表回顾。根据患者的临床表型和家族史进行基因检测，包括靶向突变检测。下一代测序，或全外显子组测序（独奏或三重奏）。作者使用PubMed对所有先前报道的与UAE的NSHL基因相关的文章进行了文献综述。
共有162例HL患者，在2010年1月至2020年12月期间进行了评估。有82例NSHL患者，本回顾性研究仅包括72例完成基因评估的患者.在研究组中，男性42人（51.2%），女性40人（48.78%）。年龄最小的患者为2岁，年龄最大的患者为50岁。76例患者（92.68％）有血缘关系。这里报道的总共14个突变是新的(23/72即，31.9%）。十二个错义突变，6个无意义的突变，6移码突变，2个框内缺失突变，发现1个剪接位点突变。GJB2基因的变异是NSHL最常见的病因，c.35delG是最多的，其次是c.506G>A。第二个常见的变体是c.934C>G（p。Arg312Gly）在CDC14A基因中，在9名患者中发现。其次是OTOF和SLC26A4基因的变异，在8名患者中发现，分别。在3例患者中发现了包含引起NSHL的基因的染色体微缺失。在该研究组中未发现线粒体突变。回顾了以前关于阿联酋NSHL患者的11份报告，共35名患者。
阿联酋NSHL患者有几种突变，最值得注意的是错义突变。新的突变值得进一步测试，代表了未来研究的领域。
