一个印度家庭中外眼肌先天性纤维化的临床表型与连锁分析

Clinical phenotype and linkage analysis of the congenital fibrosis of the extraocular muscles in an Indian family.

作者信息

Venkatesh C P, Pillai V S, Raghunath A, Prakash V S, Vathsala R, Pericak-Vance Margaret A, Kumar A

机构信息

Minto Eye Hospital, Bangalore, India.

出版信息

Mol Vis. 2002 Aug 14;8:294-7.

PMID:12181522

Abstract

PURPOSE

To describe the clinical phenotype and linkage analysis of the congenital fibrosis of the extraocular muscles (CFEOM) in an Indian family.

METHODS

Individuals were examined and their peripheral blood samples were withdrawn for genetic analysis. The disorder was tested for linkage to two known autosomal dominant CFEOM loci on chromosome 12p11.2-q12 (CFEOM1) and chromosome 16q24 (CFEOM3) using microsatellite markers.

RESULTS

Nine individuals including seven affecteds participated in the study. All seven affecteds had a classic form of CFEOM which included congenital bilateral ptosis, hypotropia, and chin elevation. The disorder segregated as an autosomal dominant trait in this family. The maximum simulated lod score in this family was 2.02. Linkage to CFEOM3 was excluded (Z<-2.00), whereas analysis of chromosome 12 markers was positive. The maximum observed two-point lod score was 1.8 (given the size and structure of the family) at theta=0 with marker D12S345. Markers D12S61, D12S1631, D12S87, D12S345, D12S59, D12S1048, and D12S1668 cosegregated with the disease locus in all affecteds. Haplotype analysis showed that the candidate region spanned the centromere.

CONCLUSIONS

The present data showed a classic CFEOM phenotype in an Indian family. The family's phenotype is consistent with linkage to CFEOM1 locus on chromosome 12p11.2-q12.

摘要

目的

描述一个印度家庭中外眼肌先天性纤维化（CFEOM）的临床表型及连锁分析。

方法

对个体进行检查，并采集其外周血样本进行基因分析。使用微卫星标记检测该疾病与12号染色体p11.2 - q12区域的两个已知常染色体显性CFEOM位点（CFEOM1）以及16号染色体q24区域（CFEOM3）的连锁情况。

结果

九名个体参与了研究，其中七名患病。所有七名患者均表现为典型的CFEOM形式，包括先天性双侧上睑下垂、下斜视和颏部抬高。该疾病在这个家族中呈常染色体显性遗传。这个家族中的最大模拟对数优势分数为2.02。排除了与CFEOM3的连锁关系（Z < -2.00），而对12号染色体标记的分析呈阳性。在θ = 0时，与标记D12S345的最大两点对数优势分数为1.8（考虑到家族的大小和结构）。标记D12S61、D12S1631、D12S87、D12S345、D12S59、D12S1048和D12S1668在所有患者中均与疾病位点共分离。单倍型分析表明候选区域跨越着丝粒。