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Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-07-20 , DOI: 10.1111/cge.13817
Zippora Brownstein 1 , Suleyman Gulsuner 2 , Tom Walsh 2 , Fábio T A Martins 1 , Shahar Taiber 1 , Ofer Isakov 3 , Ming K Lee 2 , Mor Bordeynik-Cohen 1 , Maria Birkan 1, 4 , Weise Chang 5 , Silvia Casadei 2 , Nada Danial-Farran 1, 6, 7 , Amal Abu-Rayyan 1, 8 , Ryan Carlson 2 , Lara Kamal 8 , Asgeir Ö Arnthórsson 9 , Meirav Sokolov 1, 10 , Dror Gilony 1, 10 , Noga Lipschitz 1, 11 , Moshe Frydman 1, 12 , Bella Davidov 4 , Michal Macarov 13 , Michal Sagi 13 , Chana Vinkler 14 , Hana Poran 12 , Reuven Sharony 15 , Nadra Samra 16 , Na'ama Zvi 13 , Hagit Baris-Feldman 17 , Amihood Singer 18 , Ophir Handzel 19 , Ronna Hertzano 20 , Doaa Ali-Naffaa 1, 21 , Noa Ruhrman-Shahar 4 , Ory Madgar 11 , Efrat Sofrin-Drucker 4 , Amir Peleg 21 , Morad Khayat 6 , Mordechai Shohat 1, 22, 23 , Lina Basel-Salmon 1, 4 , Elon Pras 1, 12 , Dorit Lev 1, 14 , Michael Wolf 11 , Eirikur Steingrimsson 9 , Noam Shomron 3 , Matthew W Kelley 5 , Moien N Kanaan 8 , Stavit Allon-Shalev 6, 7 , Mary-Claire King 2 , Karen B Avraham 1
Affiliation  

Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness‐associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity. Genomic DNA samples from informative relatives of 88 multiplex families, all of self‐identified Jewish ancestry, with either non‐syndromic or syndromic hearing loss, were sequenced for known and candidate deafness genes using the HEar‐Seq gene panel. The genetic causes of hearing loss were identified for 60% of the families. One gene was encountered for the first time in human hearing loss: ATOH1 (Atonal), a basic helix‐loop‐helix transcription factor responsible for autosomal dominant progressive hearing loss in a five‐generation family. Our results show that genomic sequencing with a gene panel dedicated to hearing loss is effective for genetic diagnoses in a diverse population. Comprehensive sequencing enables well‐informed genetic counseling and clinical management by medical geneticists, otolaryngologists, audiologists, and speech therapists and can be integrated into newborn screening for deafness.

中文翻译:


以色列犹太人遗传性听力损失基因谱,包括新型人类耳聋基因 ATOH1



超过 150 个基因的突变导致遗传性听力损失,其中数千种不同的严重因果等位基因在不同人群中存在差异。以色列犹太人口包括不同地理起源的社区,揭示了广泛的耳聋相关变异,并能够对相关表型进行临床表征。我们的目标是确定该人群遗传性听力损失的遗传原因,并确定基因型、表型和种族之间的关系。使用 HEar‐Seq 基因组对来自 88 个多重家庭的信息丰富的亲属的基因组 DNA 样本进行了测序,以查找已知和候选的耳聋基因,这些样本均具有自我鉴定的犹太血统,患有非综合征性或综合征性听力损失。 60% 的家庭已确定听力损失的遗传原因。首次在人类听力损失中遇到一个基因: ATOH1 (无调性),一种基本的螺旋-环-螺旋转录因子,导致五代家庭中常染色体显性进行性听力损失。我们的结果表明,使用专门针对听力损失的基因组进行基因组测序对于不同人群的基因诊断是有效的。全面的测序可以让医学遗传学家、耳鼻喉科医生、听力学家和言语治疗师提供明智的遗传咨询和临床管理,并且可以整合到新生儿耳聋筛查中。
更新日期:2020-09-23
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