中华耳科学杂志
中華耳科學雜誌
중화이과학잡지
CHINESE JOURNAL OF OTOLOGY
2013年
3期
340-344
,共5页
卢宇%张旭%燕志强%王燕飞%郑龙燕%郭菲菲%程静%韩东一%陈晓巍%袁慧军
盧宇%張旭%燕誌彊%王燕飛%鄭龍燕%郭菲菲%程靜%韓東一%陳曉巍%袁慧軍
로우%장욱%연지강%왕연비%정룡연%곽비비%정정%한동일%진효외%원혜군
常染色体显性遗传%耳聋%全外显子组测序%ACTG1
常染色體顯性遺傳%耳聾%全外顯子組測序%ACTG1
상염색체현성유전%이롱%전외현자조측서%ACTG1
DFNA%hearing loss%Whole Exome Sequencing%ACTG1
目的分析一个遗传性非综合征型耳聋家系的临床听力学特征，应用全外显子组测序技术鉴定该家系的致聋基因。方法通过家系调查，对一个感音神经性聋家系进行临床资料的收集、整理及临床听力学和遗传学特征分析，对家系成员进行调查并绘制系谱图。对2名患病的家系成员进行全外显子组测序确定候选基因，对所有家系成员进行候选基因突变的Sanger测序验证。结果该耳聋家系遗传方式为常染色体显性遗传，患者表现为迟发性、渐进性、早期以高频下降为主的听力损失，全外显子组测序提示已知耳聋基因ACTG1第4外显子存在c.364A>G杂合突变，并引起编码蛋白p.I122V的改变，该位点在多物种之间保守，Sanger测序确认该位点突变与此家系耳聋表型共分离。ACTG1编码的γ-肌动蛋白I122位点的改变可能破坏肌动蛋白纤维的组装，从而影响内耳毛细胞的静纤毛结构和功能。结论该耳聋家系为常染色体显性遗传方式，已知耳聋基因ACTG1第4外显子c.364A>G（p.I122V）突变为该耳聋家系的致病原因。
目的分析一箇遺傳性非綜閤徵型耳聾傢繫的臨床聽力學特徵，應用全外顯子組測序技術鑒定該傢繫的緻聾基因。方法通過傢繫調查，對一箇感音神經性聾傢繫進行臨床資料的收集、整理及臨床聽力學和遺傳學特徵分析，對傢繫成員進行調查併繪製繫譜圖。對2名患病的傢繫成員進行全外顯子組測序確定候選基因，對所有傢繫成員進行候選基因突變的Sanger測序驗證。結果該耳聾傢繫遺傳方式為常染色體顯性遺傳，患者錶現為遲髮性、漸進性、早期以高頻下降為主的聽力損失，全外顯子組測序提示已知耳聾基因ACTG1第4外顯子存在c.364A>G雜閤突變，併引起編碼蛋白p.I122V的改變，該位點在多物種之間保守，Sanger測序確認該位點突變與此傢繫耳聾錶型共分離。ACTG1編碼的γ-肌動蛋白I122位點的改變可能破壞肌動蛋白纖維的組裝，從而影響內耳毛細胞的靜纖毛結構和功能。結論該耳聾傢繫為常染色體顯性遺傳方式，已知耳聾基因ACTG1第4外顯子c.364A>G（p.I122V）突變為該耳聾傢繫的緻病原因。
목적분석일개유전성비종합정형이롱가계적림상은역학특정，응용전외현자조측서기술감정해가계적치롱기인。방법통과가계조사，대일개감음신경성롱가계진행림상자료적수집、정리급림상은역학화유전학특정분석，대가계성원진행조사병회제계보도。대2명환병적가계성원진행전외현자조측서학정후선기인，대소유가계성원진행후선기인돌변적Sanger측서험증。결과해이롱가계유전방식위상염색체현성유전，환자표현위지발성、점진성、조기이고빈하강위주적은력손실，전외현자조측서제시이지이롱기인ACTG1제4외현자존재c.364A>G잡합돌변，병인기편마단백p.I122V적개변，해위점재다물충지간보수，Sanger측서학인해위점돌변여차가계이롱표형공분리。ACTG1편마적γ-기동단백I122위점적개변가능파배기동단백섬유적조장，종이영향내이모세포적정섬모결구화공능。결론해이롱가계위상염색체현성유전방식，이지이롱기인ACTG1제4외현자c.364A>G（p.I122V）돌변위해이롱가계적치병원인。
Objective To analyze the clinical audiological characters and to identify the causative gene of a Chinese family with nonsyndromic autosomal dominant inherited hearing loss. Methods Clinical audiological characteristics and inheri-tance pattern of this family were evaluated,and pedigree was drawn based on medical history investigation. Whole exome se-quencing was conducted using DNA samples of two affected members of this family. Candidate mutation was confirmed by Sanger sequencing. Results This Chinese family was characterized by late onset progressive nonsydromic sensorineural hear-ing impairment. Whole exome sequencing revealed a heterozygous missense mutation c.364A>G in exon 4 of ACTG1, causing amino acid substitution Ile to Val at a conservative position 122. The p.I122V substitution is consistent with hearing loss in this Chinese family confirmed by Sanger sequencing. The alteration of conservative residue Ile122 was predicted to damage its interaction with actin-binding proteins, which may cause disruption of hair cell organization and function. Conclusion We have identified and confirmed that the I122V mutation in ACTG1 may have caused autosomal dominant non-syndromic hear-ing impairment in a Chinese family.
