Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1.
Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1.
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以色列犹太人遗传听力损失的基因谱，包括新的人类耳聋基因ATOH1。
DOI：
10.1111/cge.13817
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发表时间：
2020-10
影响因子：
3.5
通讯作者：
Avraham KB
中科院分区：
文献类型：
--
作者：
Brownstein Z;Gulsuner S;Walsh T;Martins FTA;Taiber S;Isakov O;Lee MK;Bordeynik-Cohen M;Birkan M;Chang W;Casadei S;Danial-Farran N;Abu-Rayyan A;Carlson R;Kamal L;Arnthórsson AÖ;Sokolov M;Gilony D;Lipschitz N;Frydman M;Davidov B;Macarov M;Sagi M;Vinkler C;Poran H;Sharony R;Samra N;Zvi N;Baris-Feldman H;Singer A;Handzel O;Hertzano R;Ali-Naffaa D;Ruhrman-Shahar N;Madgar O;Sofrin-Drucker E;Peleg A;Khayat M;Shohat M;Basel-Salmon L;Pras E;Lev D;Wolf M;Steingrimsson E;Shomron N;Kelley MW;Kanaan MN;Allon-Shalev S;King MC;Avraham KB
超过150个基因的突变是导致遗传性听力损失的原因，其中数千个不同的严重致病等位基因在人群中存在差异。以色列犹太人口包括不同地理来源的社区，揭示了广泛的遗传相关变异，并使相关表型的临床表征。我们的目标是确定该人群中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，这些家庭均自认为是犹太血统，患有非综合征性或综合征性听力损失。60%的家庭确定了听力损失的遗传原因。在人类听力损失中首次发现了一个基因：ATOH 1（Atonal），一种基本的螺旋-环-螺旋转录因子，在一个五代家族中负责常染色体显性进行性听力损失。我们的研究结果表明，基因组测序与专门用于听力损失的基因面板是有效的遗传诊断在不同的人群。综合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充分知情的遗传咨询和临床管理，并可整合到新生儿耳聋筛查中。
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 demonstrate 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.
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DOI：
10.1038/s41431-018-0218-z
发表时间：
2018-12
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Danial-Farran N;Brownstein Z;Gulsuner S;Tammer L;Khayat M;Aleme O;Chervinsky E;Zoubi OA;Walsh T;Ast G;King MC;Avraham KB;Shalev SA
通讯作者：
Shalev SA
DOI：
10.1056/nejmra1616601
发表时间：
2017-12-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cunningham LL;Tucci DL
通讯作者：
Tucci DL
DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
BenArie, N;Bellen, HJ;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
9.8
作者：
Azaiez H;Booth KT;Ephraim SS;Crone B;Black-Ziegelbein EA;Marini RJ;Shearer AE;Sloan-Heggen CM;Kolbe D;Casavant T;Schnieders MJ;Nishimura C;Braun T;Smith RJH
通讯作者：
Smith RJH