中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2012年
1期
78-81
,共4页
闫乃红%王云%向浩天%马用信%刘旭阳%蔡素萍
閆迺紅%王雲%嚮浩天%馬用信%劉旭暘%蔡素萍
염내홍%왕운%향호천%마용신%류욱양%채소평
人类配对盒基因%先天性无虹膜%聚合酶链反应%基因突变
人類配對盒基因%先天性無虹膜%聚閤酶鏈反應%基因突變
인류배대합기인%선천성무홍막%취합매련반응%기인돌변
Human paired box gene%Aniridia%Polymerase chain reaction%Gene mutation
背景 人类配对盒基因(PAX6)编码一个转录调节子,对眼和大脑形态的形成起关键作用.PAX6突变可导致许多先天性眼部发育异常,如先天性无虹膜症,通常为常染色体显性遗传方式. 目的 对三个先天性无虹膜症家系成员进行PAX6基因分析,探索这些家系发病的遗传基础. 方法 收集三个先天性无虹膜症家系的5例患病者和正常成员13名的外周血标本提取DNA,根据PAX6基因的序列设计4～ 13外显子序列,通过聚合酶链反应(PCR)扩增引物并测序,将目标序列与已发表的PAX6基因序列进行对比分析.结果 三个家系中共有5例患病者,在家系A中2例患者发现一个杂合突变(c.718 C＞T),导致第240位氨基酸由精氨酸突变为终止密码子(p.A rg240X),而其他正常表型者未发现此突变.家系B中的患病者和正常成员均未检测到PAX6基因的突变.家系C中1例患病者发现c.331 delG(p.Val111SerfsX13)的缺失突变,此单个碱基的缺失造成了移码突变,使PAX6蛋白羧基端的299个氨基酸缺失,而此家系的其他正常表型成员未发现此突变. 结论 家系A和家系C先天性无虹膜症的致病与PAX6基因的突变有关.
揹景 人類配對盒基因(PAX6)編碼一箇轉錄調節子,對眼和大腦形態的形成起關鍵作用.PAX6突變可導緻許多先天性眼部髮育異常,如先天性無虹膜癥,通常為常染色體顯性遺傳方式. 目的 對三箇先天性無虹膜癥傢繫成員進行PAX6基因分析,探索這些傢繫髮病的遺傳基礎. 方法 收集三箇先天性無虹膜癥傢繫的5例患病者和正常成員13名的外週血標本提取DNA,根據PAX6基因的序列設計4～ 13外顯子序列,通過聚閤酶鏈反應(PCR)擴增引物併測序,將目標序列與已髮錶的PAX6基因序列進行對比分析.結果 三箇傢繫中共有5例患病者,在傢繫A中2例患者髮現一箇雜閤突變(c.718 C＞T),導緻第240位氨基痠由精氨痠突變為終止密碼子(p.A rg240X),而其他正常錶型者未髮現此突變.傢繫B中的患病者和正常成員均未檢測到PAX6基因的突變.傢繫C中1例患病者髮現c.331 delG(p.Val111SerfsX13)的缺失突變,此單箇堿基的缺失造成瞭移碼突變,使PAX6蛋白羧基耑的299箇氨基痠缺失,而此傢繫的其他正常錶型成員未髮現此突變. 結論 傢繫A和傢繫C先天性無虹膜癥的緻病與PAX6基因的突變有關.
배경 인류배대합기인(PAX6)편마일개전록조절자,대안화대뇌형태적형성기관건작용.PAX6돌변가도치허다선천성안부발육이상,여선천성무홍막증,통상위상염색체현성유전방식. 목적 대삼개선천성무홍막증가계성원진행PAX6기인분석,탐색저사가계발병적유전기출. 방법 수집삼개선천성무홍막증가계적5례환병자화정상성원13명적외주혈표본제취DNA,근거PAX6기인적서렬설계4～ 13외현자서렬,통과취합매련반응(PCR)확증인물병측서,장목표서렬여이발표적PAX6기인서렬진행대비분석.결과 삼개가계중공유5례환병자,재가계A중2례환자발현일개잡합돌변(c.718 C＞T),도치제240위안기산유정안산돌변위종지밀마자(p.A rg240X),이기타정상표형자미발현차돌변.가계B중적환병자화정상성원균미검측도PAX6기인적돌변.가계C중1례환병자발현c.331 delG(p.Val111SerfsX13)적결실돌변,차단개감기적결실조성료이마돌변,사PAX6단백최기단적299개안기산결실,이차가계적기타정상표형성원미발현차돌변. 결론 가계A화가계C선천성무홍막증적치병여PAX6기인적돌변유관.
Background Human paired box gene 6 (PAX6) encodes a transcriptional regulator.It is essential for eye and brain morphogenesis.Mutation of PAX6 gene is responsible for many congenital ocular malformations,such as aniridia.Aniridia is a autosomal dominant inheritance mode. Objective In this study,PAX6 gene mutation was analyzed in three Chinese families with aniridia through polymerase chain reaction (PCR) and sequencing. Methods The blood specimens were collected from 5 suffers and normal individuals of 3 aniridia families to extract DNA.The sequences of extron 4-13 were designed based on PAX6 gene.The primer was amplified by PCR and sequenced and compared with the known PAX6 gene sequence.This study complied with Declaration of Helsinki and approved by ethic committee of Sichuan University.Written informed consent was obtained from each individual before any medial examination. Results There were 5 suffers in the 3 families.A heterozygous mutation (c.718 C＞T) in PAX6 gene was identified in 2 patients of family A.This mutation caused an amino acid substitution of arginine to termination codon at position 240 ( p.Arg240X) of PAX6 protein.No similar change in the normal families.No any the alteration of PAX6 gene was detected in family B whatever suffers and normal individuals.In family C,a deletion mutation of c.331 delG ( p.Val111 SerfsX13 ) in PAX6 gene was found.The deletion of one base caused frame shift mutation of PAX6 protein,and no such mutation was seen in other families. Conclusions Mutation of PAX6 gene appeares to be causative mutations of the disease in family A and C.
