日本Fuchs内皮营养不良和后多形性营养不良患者COL8A2基因突变分析

Analysis of COL8A2 gene mutation in Japanese patients with Fuchs' endothelial dystrophy and posterior polymorphous dystrophy.

作者信息

Kobayashi Akira, Fujiki Keiko, Murakami Akira, Kato Takuji, Chen Li-Zhong, Onoe Hitoshi, Nakayasu Kiyoo, Sakurai Mayumi, Takahashi Mami, Sugiyama Kazuhisa, Kanai Atsushi

机构信息

Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

出版信息

Jpn J Ophthalmol. 2004 May-Jun;48(3):195-8. doi: 10.1007/s10384-003-0063-6.

DOI:10.1007/s10384-003-0063-6

PMID:15175909

Abstract

PURPOSE

To determine whether Japanese patients with Fuchs' endothelial corneal dystrophy (FECD) and posterior polymorphous dystrophy (PPMD) carry mutations in the COL8A2 gene, and to investigate the possible pathogenicity of the COL8A2 gene in these corneal dystrophies.

METHODS

DNA analysis of the COL8A2 gene was performed in 15 unrelated Japanese patients with FECD, and 5 patients with PPMD using polymerase chain reaction and direct sequencing. Mutation screenings were also performed in 36 unrelated normal volunteers as controls, as well as slit-lamp and specular microscopy.

RESULTS

Two types of heterozygous missense mutations of the COL8A2 gene (R155Q and T502M) in 5 of 15 FECD probands (R155Q, 3/30 chromosomes, 10.0%; T502M, 3/30 chromosomes, 10.0%) were found. No mutation was detected in the coding region of the COL8A2 gene in the remaining 10 patients with FECD nor in any of the 5 patients with PPMD. These two mutations were also found in normal Japanese volunteers (R155Q, 5/72 chromosomes, 6.9%; T502M, 11/70 chromosomes, 15.7%). The chromosomal frequency of the two mutations was not significant between the patients and normal controls.

CONCLUSIONS

The R155Q and T502M mutations of COL8A2 may not be the causative defect in the Japanese FECD and PPMD patients examined in this study.

摘要

目的

确定患有富克斯角膜内皮营养不良（FECD）和后极性多形性营养不良（PPMD）的日本患者是否携带COL8A2基因突变，并研究COL8A2基因在这些角膜营养不良中的可能致病性。

方法

对15例无亲缘关系的日本FECD患者和5例PPMD患者进行COL8A2基因的DNA分析，采用聚合酶链反应和直接测序法。还对36例无亲缘关系的正常志愿者作为对照进行了突变筛查，并进行了裂隙灯和角膜内皮显微镜检查。

结果

在15例FECD先证者中的5例（R155Q，占3/30条染色体，10.0%；T502M，占3/30条染色体，10.0%）发现了COL8A2基因的两种杂合错义突变。其余10例FECD患者以及5例PPMD患者中均未在COL8A2基因编码区检测到突变。在正常日本志愿者中也发现了这两种突变（R155Q，占5/72条染色体，6.9%；T502M，占11/70条染色体，15.7%）。患者与正常对照之间这两种突变的染色体频率无显著差异。