先天性眼组织缺损一家系基因排除定位研究

Exclusive mapping for all known locus linked with congenital iris and retinochoroidal coloboma in a Chinese family

目的对1个3代常染色体显性遗传性先天性眼组织缺损家系进行致病基因的定位。方法对家系所有成员进行详细的临床检查,排除其他系统疾患。提取家系成员外周血DNA,选取20个位于4、7、10、11号染色体上已知与先天性眼组织缺损相关的4个致病基因及已知基因位点20q13.1附近的微卫星标记物进行多重PCR扩增,经ABI3130型遗传分析仪,Genscan2.1收集数据,Genotyper2.1进行基因分型,Linkage软件计算两点LOD值。研究过程遵循赫尔辛基宣言。结果未发现所选微卫星位点与该家系疾病表型共分离,LOD值均为负值。致病基因与已知的先天性眼组织缺损候选基因不存在连锁关系。结论该家系的遗传与目前已知的致病基因无关,是否存在新的致病基因有待进一步研究。

BackgroundCongenital retinochoroidal coloboma is a congenital abnormality caused by fetal cleft dysraphism with the incidence of 0.14%.It has been verified that four disease-causing genes（PAX2,PAX6,NKX5-3,SHH）and 1 locus（20q13.1）are associated with autosomal dominant congenital retinaochoroidal coloboma.ObjectiveThis study was to investigate the responsible gene for a Chinese family with autosomal dominant congenital retinaochoroidal coloboma.MethodsA detailed clinical ophthalmic examination was performed for all the members from congenital iris and retinaochoroidal coloboma family in Peking University Eye Center.The genomic DNA of all families was extracted from peripheral blood leukocytes.Twenty microsatellite markers near known candidate genes were used as genetic markers.Two-point LOD scores were calculated using the LINKAGE program（version 5.1）.This study was approved by Ethic Committee of this hospital.Written informed consent was obtained from each subject prior to any medical protocol.ResultsThe inheritance pattern of this family coincided with autosomal dominant hereditary fashion.Retinochoroidal coloboma associated with iridocoloboma in simple eye was found in 7 members.All selected microsatellite markers were not cosegregated with the phenotype in this family.LOD scores were negative.ConclusionAll known autosomal dominant congenital retinaochoroidal coloboma locus are excluded in this family.Further genetic screen should been executed to search the possible causative gene or locus in this family.