A novel EYA4 mutation causing hearing loss in a Chinese DFNA family and genotype-phenotype review of EYA4 in deafness.
A novel EYA4 mutation causing hearing loss in a Chinese DFNA family and genotype-phenotype review of EYA4 in deafness.
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中国DFNA家系引起听力损失的EYA4新突变及EYA4在耳聋中的基因型-表型评价
DOI：
10.1186/s12967-015-0483-3
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发表时间：
2015-05-12
影响因子：
7.4
通讯作者：
Dai P
中科院分区：
文献类型：
--
作者：
Huang A;Yuan Y;Liu Y;Zhu Q;Dai P
背景：遗传性听力损失是一类异质性疾病，表现出多种遗传模式并涉及许多基因。 EYA4 基因的突变导致 DFNA10 基因座的舌后、进行性、常染色体显性听力损失。方法：我们报告了一个患有感音神经性、进行性听力损失的中国家庭。使用该家族的 DNA 样本进行了下一代测序 (NGS)。桑格测序证实了候选突变。提供了耳聋中 EYA4 的详细基因型和表型分析。结果：NGS 显示所有受影响的家庭成员的 EYA4 外显子 8 中存在插入突变 c.544_545insA。该插入产生移码，导致在位置 221 (p.F221X) 处出现终止密码子。 p.F221X 移码突变与家族中的听力损失共分离。受影响的家庭成员的听力图是平坦的或倾斜的，与特征性的“饼干咬”听力图不同，并且该突变位于EYA4中eyaHR的不同区域。结论：我们在EYA4基因中发现了一种新的移码突变。我们的结果丰富了 EYA4 的突变谱，并突出了 DFNA10 基因型和表型的复杂性。利用NGS技术建立听力损失患者常见突变数据库并进一步积累数据，将有助于遗传性听力损失的早期诊断和基础治疗的开发。
Background:Hereditary hearing loss is a heterogeneous class of disorders showing various patterns of inheritance and involving many genes. Mutations in the EYA4 gene are responsible for postlingual, progressive, autosomal dominant hearing loss at the DFNA10 locus.Methods:We report on a Chinese family with sensorineural, progressive hearing loss. Next-generation sequencing (NGS) was conducted using DNA samples from this family. A candidate mutation was confirmed by Sanger sequencing. A detailed genotype and phenotype analysis of EYA4 in deafness is provided.Results:NGS revealed an insertion mutation c.544_545insA in exon 8 of EYA4 in all affected family members. This insertion created a frameshift resulting in a stop codon at position 221 (p.F221X). The p.F221X frameshift mutation cosegregated with hearing loss in the family. Audiograms of affected family members are flat or sloping, differing from the characteristic "cookie bite" audiogram and the mutation is localized in a different region of the eyaHR in EYA4.Conclusions:We identified a novel frameshift mutation in the EYA4 gene. Our results enrich the mutational spectrum of EYA4 and highlight the complexity of the DFNA10 genotypes and phenotypes. Using NGS techniques to establish a database of common mutations in patients with hearing loss and further data accumulation will contribute to the early diagnosis and development of fundamental therapies for hereditary hearing loss.
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影响因子：
3.7
作者：
Baek JI;Oh SK;Kim DB;Choi SY;Kim UK;Lee KY;Lee SH
通讯作者：
Lee SH
影响因子：
10.5
作者：
Heanue, TA;Reshef, R;Tabin, CJ
通讯作者：
Tabin, CJ
影响因子：
2
作者：
Hildebrand, Michael S.;Coman, David;Dahl, Hans-Henrik M.
通讯作者：
Dahl, Hans-Henrik M.
I411K 的鉴定，这是一种导致常染色体显性非综合征性听力损失的新型错义 EYA4 突变
影响因子：
5.4
作者：
Tan, Minxing;Shen, Xiaofei;Xing, Guangqian
通讯作者：
Xing, Guangqian
影响因子：
3.5
作者：
ONeill, ME;Marietta, J;Smith, RJH
通讯作者：
Smith, RJH