一个非典型Reis-Bückler角膜营养不良家系的TGFBI基因突变研究

Analysis of TGFBI gene mutation in a Chinese family with atypical Reis-Biickler corneal dystrophy

目的通过基因突变分析，确定一个非典型Reis-Biickler角膜营养不良家系突变基因型和表现型之间的关系。方法采集家系中的4例患者及2名健康成员和100名正常对照的外周血10mL，提取白细胞DNA，应用聚合酶链反应分别扩增TGFBI基因的第4、11、12、14外显子，并对扩增产物进行直接测序分析。结果发现TGFBI基因第623密码子第2个碱基呈杂合性点突变G-A，导致甘氨酸突变为天冬氨酸（P．G623D），家系中健康成员和正常对照均未检测到此突变存在。结论这一由TGFBI基因G623D突变引起的角膜营养不良为非典型的ReisBiickler角膜营养不良，这在我国属首次报告。

Objective To identify the TGFBI gene mutation and the relationship between genotype and phenotype of a Chinese family with atypical Reis-Bfickler corneal dystrophy （RBCD）. Methods Four patients, two non carrier relatives of the family were enrolled in the present study. In addition to ophthalmologie examinations, PCR amplification and DNA sequencing of exons 4, 11, 12, and 14 of the TGFBI gene were carried out. Exon 14 was also sequenced in 100 healthy controls. Results A G to A transition at codon 623 in all affected members was identified. This mutation resulted in a substitution of glycine （GGC） to aspartic acid （GAC） at the protein level. None of the healthy family members, or any of the 100 control subjects carried this mutation. Conclusion The G623D mutation of the TGFBI gene caused an atypical Reis-Btickler corneal dystrophy in this family. This mutation is reported in Chinese for the first time.