一个X连锁遗传性耳聋2型致病基因POU3F4新突变致多系统临床表现的研究  

A Study on a Novel POU3F4 Mutation Associated with X-linked inheritance deafness-2 Leading to Multisystem Clinical Manifestations

作　　者：刘硕 齐心 黄莎莎[1,3] 戴朴 张帆[5] 苏钰 LIU Shuo;QI Xin;HUNG Shasha;DAI Pu;ZHANG Fan;SU Yu(College of Otolaryngology Head and Neck Surgery,Chinese PLA General Hospital,Beijing 100853,China;不详)

机构地区：[1]中国人民解放军总医院耳鼻咽喉头颈外科医学部,北京100048 [2]中国人民解放军总医院海南医院耳鼻咽喉头颈外科 [3]国家耳鼻咽喉疾病临床医学研究中心 [4]海南省耳鼻咽喉头颈疾病临床医学研究中心 [5]中国人民解放军总医院海南医院放射诊断科

出　　处：《中华耳科学杂志》2025年第2期240-247,共8页Chinese Journal of Otology

基　　金：国家耳鼻咽喉疾病临床医学研究中心开放课题(202200012);海南省自然科学基金重点研发计划(ZDYF2020142);国家自然科学基金青年项目(81400471)。

摘　　要：目的研究POU3F4基因新突变在不完全分隔Ⅲ型内耳畸形中的致病作用及与多系统功能障碍的关系。方法对先证者进行详细的病史采集、全面的体格检查、听力学评估、影像学检查、激素水平检测,以及全外显子测序和家系验证。结果该家系符合X连锁隐性遗传模式,先证者听力学表现为双侧极重度感音神经性聋,影像学显示典型的不完全分隔Ⅲ型内耳畸形,同时伴有生长发育迟缓、睾丸发育不全、垂体高度减小、注意力缺陷等内分泌和神经发育问题。实验室检查显示先证者下丘脑-垂体-内分泌轴的多项功能异常。全外显子测序发现了POU3F4基因的新突变c.401_404dup(p.Gln136Leufs*58),符合基因型与表型共分离。结论POU3F4基因变异可能导致多系统功能障碍,但POU3F4基因变异相关的综合征性听力损失的定义和治疗策略尚需要进一步研究和验证。Objective The aim is to investigate the pathogenic role of a novel POU3F4 mutation in incomplete partition typeⅢ(IP-Ⅲ)and its association with multisystem dysfunction.Methods Comprehensive evaluations were conducted on the proband,including detailed medical history collection,thorough physical examinations,audiological assessments,radiological tests,hormone level testing,whole-exome sequencing,and family segregation analysis.Results The pedigree was consistent with an X-linked recessive inheritance pattern.The proband exhibited bilateral profound sensorineural hearing loss,with imaging revealing typical incomplete partition typeⅢ.Additionally,the proband presented with growth retardation,testicular hypoplasia,reduced pituitary height,and neurodevelopmental issues such as attention deficit.Laboratory findings indicated multiple functional abnormalities along the hypothalamic-pituitary-endocrine axis.Whole-exome sequencing identified a novel POU3F4 mutation,c.401_404dup(p.Gln136Leufs*58),which was consistent with genotypic and phenotypic co-segregation.Conclusion POU3F4 mutations may result in multisystem dysfunction.However,the definition and treatment strategies for syndromic hearing loss associated with POU3F4 mutations require further investigation and validation.

关 键 词：X连锁遗传性耳聋2型 POU3F4基因 不完全分隔Ⅲ型内耳畸形 多系统临床症状 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]