Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation
Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation
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患有新型 POU3F4 突变和不完全分区 III 型畸形患者的人工耳蜗植入
DOI：
10.1155/2020/8829587
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发表时间：
2020-09-01
影响因子：
3.1
通讯作者：
Xu, Lei
中科院分区：
文献类型：
--
作者：
Chao, Xiuhua;Xiao, Yun;Xu, Lei
本研究旨在(1)分析一个非综合征性x连锁隐性听力损失家族中一个新的POU3F4突变的临床表现和遗传特征，(2)报道该突变患者的人工耳蜗植入结果。方法1例诊断为IP-III型畸形的患者在我院行人工耳蜗植入术。对其家族进行遗传分析，包括全外显子组测序结合Sanger测序和生物信息学分析。评估先证者及其家庭的临床特征、术前听觉和言语表现以及人工耳蜗（CI）术后预后。结果在该家族中检测到POU3F4基因c.400_401insACTC新变异（p.Q136LfsX58），该变异与听力损失共分离。200名听力正常的人没有这种变异。Pou3f4蛋白的系统发育分析和结构建模进一步证实了该突变具有致病性。先证者在四岁时接受了右耳人工耳蜗植入，听力和语言有了很大的改善。然而，CI的益处在术后约三年半下降。虽然右耳已经重新植入，但结果仍然比以前更糟。结论在中国一个x连锁遗传性听力损失家庭中发现了POU3F4基因的一个新的帧移变异c.400_401insACTC （p.Q136LfsX58）。具有这种突变和IP-III畸形的患者可以从CI中获得良好的益处。然而，随着患者年龄的增长，人工耳蜗植入的效果可能会下降。
Aims This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.