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目的分析一个遗传性聋伴前庭功能障碍家系的表型特征,并探讨该家系的相关致病基因。方法对门诊发现的1例渐进性聋伴眩晕患者进行家系调查、病史资料采集、常规检查、听力学及前庭功能检查。听力学检查包括纯音测听、声导抗,前庭功能检查为冷热水试验。采集家系成员外周血DNA,采用聚合酶链反应(poly-merase chain reaction,PCR)扩增-直接测序法对POU3F4基因和COCH基因进行全部编码序列突变检测。结果该家系共4代28人,现存3代26人,主诉听力障碍者4人,耳聋患者均为正常女性后代中的男性,表现出隔代交叉遗传特征。耳聋患者出生时听力正常,6~10岁出现听力减退,并同时出现眩晕,走路不稳感。其中2人听力快速恶化,言语能力差,纯音测听为双耳对称的重度-极重度感音神经性听力损失,另外2人表现为高频下降型听力曲线。4名耳聋患者前庭功能低下或丧失。家系成员基因测序结果显示在POU3F4基因和COCH基因中均未检测到突变。结论本研究家系为非综合征型聋并前庭功能异常的家系,符合X-连锁隐性遗传特征规律,遗传方式最终确定有赖于进一步的分子遗传学研究。该家系患者高度一致的表型特征提示为单一基因致病,但筛查目前与这一表型相关的POU3F4基因和COCH基因未发现突变,可能存在其他与这一表型相关的基因。
Objective To analyze the phenotypic characteristics of a pedigree with hereditary deafness and vestibular dysfunction and to explore the related genes of the pedigree. Methods One case of progressive deafness and vertigo found in outpatients was investigated by family history, history data collection, routine examination, audiology and vestibular function. Hearing tests include pure tone audiometry, acoustic impedance, vestibular function tests for hot and cold water tests. DNA from peripheral blood of family members was collected and all the coding sequence mutations of POU3F4 gene and COCH gene were detected by polymerase chain reaction (PCR) amplification and direct sequencing. Results The pedigree was a total of 4 generations of 28 people, the existing 3 generations of 26 people, the main complaint of hearing impaired 4 people, deaf patients were normal male offspring of men, showing inter-generational crossover genetic characteristics. Deafness at birth, normal hearing, 6 to 10 years old hearing loss, and at the same time there dizziness, walking instability. Two of them had rapid hearing loss, poor verbal ability, pure tone audiometry as severe symmetrical and severe sensorineural hearing loss, while the other two patients showed high frequency descending hearing curve. Four deaf patients had vestibular dysfunction or loss. Family members of the gene sequencing results showed that no mutations were detected in the POU3F4 gene and the COCH gene. Conclusion The pedigree of non-syndromic deafness with abnormal vestibular function is consistent with the X-linked recessive genetic characteristics. The final determination of the genetic mode depends on the further molecular genetics research. This family of patients with highly consistent phenotypic characteristics suggest a single gene pathogenicity, but the screen is currently associated with this phenotype POU3F4 gene and COCH gene found no mutation, there may be other genes associated with this phenotype.