CAJ | 학술논문

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。
목적：탐토일개새-이종합정가계적표형특정，진행후선치병기인적돌변사사。방법경지정동의，대조사대상진행전신검사이급은역학화섭골CT평고，획득혈양표본；정리분석가계자료병회제계보도；용기인조DNA제취시제합제취외주혈DNA，진행새-이-신종합정상관기인EYA1、SIX1화SIX5전편마외현자적서렬분석。결과해가계공4대31인，7인구유새-이-신종합정상관증상，계보분석부합상염색체현성유전특정。6명환자주소은력하강，위최상견림상표현，기타증상유이전루관2인차、새렬루3인차화이곽기형4인차，균무신장기형표현。2명환자순음은력도시쌍이혼합성롱，섭골CT검사견중이화내이발육이상，후선치병기인사사균검측도EYA1 c.922C>T돌변。결론해가계표형특정부합새-이종합정진단，단가계내환병개체간림상표현구유이질성。EYA1 c.922C>T돌변시본가계치병적주요분자기출。
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.