先天性广泛眼外肌纤维化综合征一家系的连锁分析和候选基因研究  

The clinical manifestation and linkage analysis in one Chinese family with congenital fibrosis of extraocular muscles

作　　者：赵晨[1] 陆莎莎[2] 李宁东[1] 陈薇英[1] 赵堪兴[2] 

机构地区：[1]天津市眼科医院,300040 [2]天津医科大学

出　　处：《中华眼科杂志》2005年第7期594-599,共6页Chinese Journal of Ophthalmology

基　　金：国家自然科学基金资助项目(30070805)

摘　　要：目的探讨先天性广泛眼外肌纤维化综合征(CFEOM)一家系的临床表型特征和致病基因。方法收集CFEOM一家系,对全部患者进行临床检查和全基因组扫描及连锁分析(linkageanalysis),对连锁区域内的候选基因KIf21A进行基因序列分析。结果此家系中4例患者具有典型CFEOM临床表现。连锁分析显示微卫星标记物D12S1648、D12S345、D12S1692、D12S59、D12S1090、D12S2194、D12S1048、D12S1668在家系中与全部患者的疾病表型共分离,并在D12S1090取得最大LOD值(2.12)。KIf21A基因测序未发现突变,仅在外显子21发现一单个碱基多态性改变。结论此家系属常染色体显性遗传CFEOM1型,致病基因定位于染色体带12p11.2q12微卫星标记物D12S1648和D12S1668之间约4cM的区域。KIF21A基因可能不是此家系的致病基因。Objective To describe the clinical phenotype in a Chinese family with congenital fibrosis of extraocular muscles and to identify the location of candidate gene of the disease in chromosome. Methods The clinical feature of all affected members in this family were examined. A genome-wide linkage screening was conducted. Direct genomic sequencing was used to evaluate the candidate gene KIf21A.Results Four affected members in the pedigree were born with classic phenotype of CFEOM. By linkage analysis the disease gene was mapped to chromosomal region 12p11.2-q12 defined by microsatellite markers D12S1648 and D12S1668. The maximum Lod Score was 2.12 (D12S1090). Direct sequence showed no mutation in all exons and exon-intron boundaries of the candidate gene KIF21A, a polymorphism substitution occurred in the exon 21.Conclusions The disorder in this family should be referred as CFEOM1 which was inherited as an autosomal dominant trait. The candidate gene was linked to CFEOM1 locus on chromosome 12p11.2-q12, between marker D12S1648 and D12S1668. It′s more likely that KIf21A is not the disease causing gene in this family.

关 键 词：眼外肌纤维化 连锁分析 综合征 先天性 家系 基因研究 analysis) 常染色体显性遗传 全基因组扫描 基因序列分析 致病基因定位 中华眼科杂志 表型特征 临床检查 候选基因 临床表现 疾病表型 LOD值 基因测序 标记物 微卫星 

分 类 号：R777.4[医药卫生—眼科] R544.1[医药卫生—临床医学]