先天性广泛眼外肌纤维化综合征一家系临床表型及基因连锁定位分析

Clinical phenotype and linkage analysis in a Chinese family with congenital fibrosis of extraocular muscle

目的 分析一个先天性广泛眼外肌纤维化综合征 (CFEOM)家系的临床表型 ,并通过连锁分析方法来定位该家系的致病基因。方法 对家系中的所有患者进行临床检查。根据目前已知的两种常染色体显性遗传类型的CFEOM的遗传学位点 12p11 2 q12 (FEOM1)和 16q2 4(FEOM3 )选取微卫星进行连锁分析研究。结果 家系中 4名患者具有典型的CFEOM表现。连锁分析显示 ,微卫星D12S5 9、D12S10 48、D12S164 8在所有患者中与疾病呈现共分离现象 ,其中D12S10 48最大Lod值为 1 91,而在微卫星D12S61和D12S10 90处出现重组 ,表明该家系的致病基因位于这两个微卫星之间。结论 此家系属常染色体显性遗传的CFEOM 1型 ,其致病基因定位于 12p11 2 q12的D12S61和D12S10

Objective To describe the clinical phenotype in a Chinese family with congenital fibrosis of extraocular muscle,and determine the genetic location of the candidate gene. Methods The clinical features of all affected members in this family were determined.The family was tested for linkage analysis to two known autosomal dominant CFEOM loci on chromosome 12p11.2-q12(CFEOM1)and 16q24(CFEOM3). Results Four affected members in the pedigree had classic phenotype of CFEOM.Markers D12S59,D12S1048 and D12S1648 were co-segregated with the disease locus in all affected members.The maximum Lod Score was 1.91(D12S1048).Recombination events occurred in marker D12S61 and D12S1090. Conclusion The disorder in this family should be referred as CFEOMⅠwhich was inherited as an autosomal dominant trait.The candidate gene is linked to CFEOM1 locus on chromosome 12p11.2-q12 between marker D12S61 and D12S1090.