晶状体脱位一家系FBN1基因N1173K突变研究

摘要

目的 对常染色体显性遗传晶状体脱位( EL)一家系进行致病基因研究.方法 通过询问病史及系谱分析确定遗传模式.对所有患者进行临床检杳,包括眼部、心脏以及骨骼确定临床表型.采集患者外周静脉血5 ml,提取基因组DNA.采用微卫星标记引物,通过连锁分析进行致病基因定位,两点法计算LOD值.采用直接测序法对致病基因全部外显子,以及外显子与内含子拼接部进行基因序列分析.结果 该家系为常染色体显性遗传模式.经连锁分析,将致病基因定位于常染色体15q21.1区间,并在微卫星位点D15S978获得最大LOD值为3.01.基因序列分析发现候选基因FBN1 29外显子发生c.C3519G.(p.N1173K)杂合性基因突变,而家系正常人以及100名正常对照无此基因突变.结论 FBN1基因N1173K突变是导致该家系临床表型的主要原因.%Objective To study the disease-causing gene mutation in a Chinese family with ectopia lentis.Methods The phenotype of each family member in a Chinese family with ectopia lentis was identified by detailed clinical examination. The inheritance mode in this family was ascertained by the pedigree analysis.Linkage analysis was performed by microsatellite markers on chromosome 15 and LOD Score was calculated by Mlink program. Gene mutations were detected by sequence analysis to the whole coding region and exon-intron boundaries of the candidate gene. Results A significant LOD score of 3.01 was obtained at D15S978 on chromosome 15q21.1,where FBNI gene was located. A C3519G change in exon 29 of FBNI gene,resulting in asparagine change to lysine at codon 1173,was detected by direct sequence analysis. This mutation was absent in the normal family members and 100 normal controls.Conclusions Our results indicate that c.C3519G (p.N1173K) mutation in FBN1 gene is the underlying molecular pathogenesis of this family with ectopia lentis.(Chin J Ophthalmol,2012,48: