CAJ | 학술논문

目的寻找一个我国汉族常染色体显性遗传性白内障家系的致病基因.方法病例对照研究.收集家系的资料,用裂隙灯显微镜检查家系成员的晶状体;提取家系中参与研究的26名成员的基因组DNA,进行白内障致病基因(如晶状体蛋白基因和Cx基因等6个基因)外显子区域的突变扫描,用限制性片段长度多态性分析技术(PCR-RFLP)对检测到的突变进行验证,在42例年龄相关性白内障患者和204名正常人中检测是否存在已筛查到的突变.结果疾病的表型为粉尘状核性白内障;在Cx50基因(GJA8)的编码核苷酸序列第827位发现一个C到T的新突变,导致在Cx氨基酸序列的276位出现一个丝氨酸到苯丙氨酸的改变,氨基酸由极性中性氨基酸变成疏水性的非极性氨基酸.在42例年龄相关性白内障患者和204名正常人中均未检测到这一突变,同时在晶状体蛋白和Cx基因上发现4个单核苷酸多态性位点.结论在一个我国汉族显性遗传性白内障家系中发现一个GJA8基因的新突变(P.276 S＞F),可能是该遗传性白内障的致病基因突变.
목적 심조일개아국한족상염색체현성유전성백내장가계적치병기인.방법 병례대조연구.수집가계적자료,용렬극등현미경검사가계성원적정상체;제취가계중삼여연구적26명성원적기인조DNA,진행백내장치병기인(여정상체단백기인화Cx기인등6개기인)외현자구역적돌변소묘,용한제성편단장도다태성분석기술(PCR-RFLP)대검측도적돌변진행험증,재42례년령상관성백내장환자화204명정상인중검측시부존재이사사도적돌변.결과 질병적표형위분진상핵성백내장;재Cx50기인(GJA8)적편마핵감산서렬제827위발현일개C도T적신돌변,도치재Cx안기산서렬적276위출현일개사안산도분병안산적개변,안기산유겁성중성안기산변성소수성적비겁성안기산.재42례년령상관성백내장환자화204명정상인중균미검측도저일돌변,동시재정상체단백화Cx기인상발현4개단핵감산다태성위점.결론 재일개아국한족현성유전성백내장가계중발현일개GJA8기인적신돌변(P.276 S＞F),가능시해유전성백내장적치병기인돌변.
Objective The aim of this study was to reveal the genetic defect of the autosomal dominant inheritance cataract in a Chinese pedigree.Methods Case-control study.There were 26 individuals investigated with clinical examination in a Chinese four generations pedigree.The genome DNA of the individuals was extracted bv the improved NaI method.The exons of six cataract candidate genes in 204 normal controls and 42 senile cataract patients were screened for the mutation by PCR restriction fragment length polymorphism (PCR-RFLP) methods.Results The phenotype of the cataract was pulvemlent nuclear cataract.A novel C/T transition at nucleotide position 827 was identified in the GJA8 gene that led to a serine to phenylalanine change in coden 276.This mutation was not found in 42 senile cataract patients and in 204 controls.Four single nucleotide polymorphisms (SNPs) were also found in a cataract candidate gene in the family members.Conclusions A Hovel GJA8 gene mutation was found in a Chinese autosomal dominant inheritance cataract pedigree.A substitution.C276T in GJA8 gene.was identified as the most likely causalive mutation underlying the phenotype of pulverulent nuclear cataract in all affected family members.