先天性前极白内障家系致病基因的定位与候选基因突变检测  

Gene mapping and mutation detection in a family with congenital anterior polar cataract

作　　者：张璐[1] 刘平[1] 张毅[1] 苏胜[1] 唐先玲[1] 白洁[1] 

机构地区：[1]哈尔滨医科大学附属第一医院眼科医院,150001

出　　处：《中华眼科杂志》2011年第8期721-725,共5页Chinese Journal of Ophthalmology

基　　金：中国博士后科学基金（20080440909）;中国博士后科学基金特别资助（200902422）;黑龙江省自然科学基金（D200870）

摘　　要：目的对中国一常染色体显性遗传先天性前极白内障家系进行致病基因的定位与候选基因突变检测。方法采集家系成员外周静脉血，提取基因组DNA。选用ABI公司提供的约400个遗传标记物进行基因扫描。基因扫描分初步扫描和精细扫描两步进行。首先对已报道的先天性白内障候选区域进行初步扫描，之后在阳性区域内进行精细扫描。数据经连锁分析，初步确定致病基因所在染色体区域。在阳性区域内选取更高密度的荧光标记物进行精细扫描，并进行单体型分析。候选基因直接测序检测基因突变。结果两点间连锁分析在微卫星标记D21S1252处获得最大对数优势计分（LOD）值Zmax=3．23（θmax=0．00）。精细定位和单体型分析将致病基因定位于微卫星标记D21S263和D21S266之间，遗传距离约18．47厘摩（cM），染色体位置为21q22．11-q22．3。候选基因直接测序发现CRYAA基因第3外显子第347碱基一个G→A的点突变。结论本研究将一中国先天性前极白内障家系的致病基因定位于21号染色体21q22．11-q22．3区域内，并在CRYAA基因发现一个点突变与此家系共分离。（中华腹科杂志，2011，47：721-725）Objective To map the gene mutation responsible for autosomal dominant inherited congenital anterior polar cataract in a Chinese family. Methods Peripheral blood samples were collected from the members in this congenital cataract family. DNA was extracted from the blood samples. A genesean was performed using approximately 400 microsatellite markers （ABI）. Linkage analysis was processed to define the region of mutated gene. High density primers labeled with fluorescent stain for the positive region were adopted for fine targeting and haplotype analysis was performed. Mutation detection was carried out by sequencing candidate genes. Results The maximum two-point LOD score was obtained at D21S1252, Zmax =3. 23 （0max =0. 00）. After fine targeting and baplotype analysis, the mutated gene was located within a 18.47 cM region between D21 S263 and D21 S266 on chromosome 21q22. 11-q22. 3. Direct sequencing of the candidate gene revealed a G→ A transition in exon 3 of CRYAA. Conclusion The present study has identified a missense mutation in CRYAA associated with congenital anterior polar cataract in a Chinese family. （Chin J Ophthalmol , 2011,47：721-725）

关 键 词：白内障 染色体图 系谱 染色体 人 21对 晶体蛋白质类 突变 

分 类 号：R776.1[医药卫生—眼科]