目的：探讨一个鳃-耳综合征家系的表型特征，进行候选致病基因的突变筛查。方法经知情同意，对调查对象进行全身检查以及听力学和颞骨CT评估，获得血样标本；整理分析家系资料并绘制系谱图；用基因组DNA提取试剂盒提取外周血DNA，进行鳃-耳-肾综合征相关基因EYA1、SIX1和SIX5全编码外显子的序列分析。结果该家系共4代31人，7人具有鳃-耳-肾综合征相关症状，系谱分析符合常染色体显性遗传特征。6名患者主诉听力下降，为最常见临床表现，其它症状有耳前瘘管2人次、鳃裂瘘3人次和耳廓畸形4人次，均无肾脏畸形表现。2名患者纯音听力图示双耳混合性聋，颞骨CT检查见中耳和内耳发育异常，候选致病基因筛查均检测到EYA1 c.922C>T突变。结论该家系表型特征符合鳃-耳综合征诊断，但家系内患病个体间临床表现具有异质性。EYA1 c.922C>T突变是本家系致病的主要分子基础。%Objective To investigate the phenotypic manifestations of branchio-otic syndrome in a Chinese family, and to search for candidate mutational genes. Methods After obtaining informed consent from the participants, medical and audio⁃logical examinations as well as CT scan of the temporal bone were performed. The inheritance mode in the family was evaluat⁃ed. Genomic DNA was isolated from peripheral leukocytes using the Puregene DNA Isolation Kits. DNA fragments spanning the whole coding regions of EYA1, SIX1 and SIX5 genes were PCR amplified and directly sequenced. Results The family had 31 members in 4 generations, of whom 7 were affected. The mode of inheritance in the family was consistent with the autosomal dominant pattern according to pedigree analysis. Hearing loss was the most common manifestation occurring in 6 patients. Oth⁃er findings included preauricular pits (n=2), cervical fistulas (n=3) and abnormal pinnae (n=4). None of the affected subjects had renal anomalies. In two patients evaluated by pure-tone audiometry and temporal bone imaging, bilateral mixed hearing loss as well as middle ear and inner ear deformities were found. Mutational analysis of candidate genes in the selected patients identified a nonsense EYA1 mutation c.922C>T. Conclusions Phenotypic manifestations in this Chinese family suggest the di⁃agnosis of branchio-otic syndrome, although the penetrance is variable within patients. The EYA1 c.922C>T mutation is the main genetic basis underlying the disease.
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