Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1,Clinical Genetics

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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

Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Departments of Genome Sciences and Medicine, University of Washington, Seattle, Washington, USA.
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Raphael Recanati Genetic Institute, Rabin Medical Center-Beilinson Hospital, Tel Aviv University Felsenstein Medical Research Center, Petach Tikva, Israel.
Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA.
Genetics Institute, Ha'Emek Medical Center, Afula, Israel.
Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Department of Biological Sciences, Bethlehem University, Bethlehem, Palestine.
Department of Biochemistry and Molecular Biology, BioMedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Department of Otolaryngology-Head and Neck Surgery, Schneider Children's Medical Center, Petach Tikva, Israel.
Department of Otolaryngology-Head and Neck Surgery, Sheba Medical Center, Tel Hashomer, Israel.
Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
Department of Human Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel.
Genetics Institute, Meir Medical Center, Kfar Saba and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ziv Medical Center, Zefat, Israel.
Genetics Institute, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Community Genetics Department, Public Health Services, Ministry of Health, Ramat Gan, Israel.
Department of Otolaryngology Head and Neck Surgery and Maxillofacial Surgery, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Human Genetics Institute, Lady Davis Carmel Medical Center, Haifa, Israel.
Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel.
Institute of Medical Genetics, Maccabi HMO, Rehovot, Israel.

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。全面的测序使医学遗传学家、耳鼻喉科医生、听力学家和语言治疗师能够进行知情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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