Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families
Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families
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多个 DFNX2 中国家族 POU3F4 突变的临床和分子特征
DOI：
10.1186/s12881-018-0630-9
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发表时间：
2018-09
影响因子：
--
通讯作者：
Pu Dai
中科院分区：
文献类型：
--
作者：
Yu Su;Xue Gao;Sha-Sha Huang;Jing-Ning Mao;Bangqing Huang;Jian-Dong Zhao;Dong-Yang Kang;Xin Zhang;Pu Dai
许多X连锁的非综合征性听力损失(HL)病例是由POU结构域3类转录因子4(POU3F4)基因的各种突变引起的。本研究旨在鉴定2个X-连锁遗传性耳聋-2(DFNX2)家系和1例散发性不明遗传模式的POU3F4基因的等位基因变异。对这些家系和100名听力正常的中国人进行POU3F4基因的直接DNA测序。DFNX2患者的颞骨CT表现为距骨底板增厚、耳蜗基底部发育不良、骨性蜗壳缺失、内耳道扩张以及内耳道与耳蜗底回之间异常广泛的交通。我们在三个先证者及其大家族中发现了POU3F4的三个致病突变。在1468家系中，我们观察到一个新的缺失突变c.973delT，该突变被预测导致p.Trp325Gly氨基酸移码。在2741号家族中，发现了突变c.927delCTC，该突变被预测会导致310位丝氨酸的缺失。在这两个家族中，突变都位于POU同源结构域，并被预测会截断POU结构域的C末端。在第三个家族中，在一名5岁男孩中发现了一种新的从头颠换突变(c.669 T>；A)，导致了一种无义突变(p.Tyr223)。该突变产生了一个新的终止密码子，预计将导致POU3F4蛋白的截短。根据DFNX2患者特有的放射学表现和临床特征，POU3F4基因突变分析将提高砧骨手术和人工耳蜗术的成功率，并改善分子诊断、遗传咨询和对HL的分子流行病学知识。
Many X-linked non-syndromic hearing loss (HL) cases are caused by various mutations in the POU domain class 3 transcription factor 4 (POU3F4) gene. This study aimed to identify allelic variants of this gene in two Chinese families displaying X-linked inheritance deafness-2 (DFNX2) and one sporadic case with indefinite inheritance pattern.Direct DNA sequencing of the POU3F4 gene was performed in these families and in 100 Chinese individuals with normal hearing.There are characteristic imaging findings in DFNX2 Chinese families with POU3F4 mutations. The temporal bone computed tomography (CT) images of patients with DFNX2 are characterized by a thickened stapes footplate, hypoplasia of the cochlear base, absence of the bony modiolus, and dilated internal acoustic meatus (IAM) as well as by abnormally wide communication between the IAM and the basal turn of the cochlea. We identified three causative mutations in POU3F4 for three probands and their extended families. In family 1468, we observed a novel deletion mutation, c.973delT, which is predicted to result in a p.Trp325Gly amino acid frameshift. In family 2741, the mutation c.927delCTC was identified, which is predicted to result in the deletion of serine at position 310. In both families, the mutations were located in the POU homeodomain and are predicted to truncate the C-terminus of the POU domain. In the third family, a novel de novo transversion mutation (c.669 T > A) was identified in a 5-year-old boy that resulted in a nonsense mutation (p.Tyr223). The mutation created a new stop codon and is predicted to result in a truncated POU3F4 protein.Based on characteristic radiological findings and clinical features, POU3F4 gene mutation analysis will increase the success rate of stapes operations and cochlear implantations, and improve molecular diagnosis, genetic counseling, and knowledge of the molecular epidemiology of HL among patients with DFNX2.
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影响因子：
--
作者：
Bademci G;Lasisi A;Yariz KO;Montenegro P;Menendez I;Vinueza R;Paredes R;Moreta G;Subasioglu A;Blanton S;Fitoz S;Incesulu A;Sennaroglu L;Tekin M
通讯作者：
Tekin M
影响因子：
2.1
作者：
CREMERS, CWRJ;HOMBERGEN, GCJH;WENTGES, RTR
通讯作者：
WENTGES, RTR
影响因子：
56.9
作者：
DEKOK, YJM;VANDERMAAREL, SM;CREMERS, FPM
通讯作者：
CREMERS, FPM
DOI：
10.1016/j.ijporl.2014.08.013
发表时间：
2014-10-01
影响因子：
1.5
作者：
Gong, Wu-Xian;Gong, Ruo-Zhen;Zhao, Bin
通讯作者：
Zhao, Bin
影响因子：
1.4
作者：
Stankovic, Konstantina M.;Hennessey, Ann Marie;Mankarious, Leila A.
通讯作者：
Mankarious, Leila A.