Best病家系卵黄样黄斑营养不良基因突变分析

目的 观察Best病家系卵黄样黄斑营养不良基因(VMD2)基因型与表现型之间的相互关系，为建立Best病基因诊断方法提供理论依据。 方法 采用聚合酶链反应（PCR）和DNA直接测序法对一个Best病家系10个成员的VMD2基因编码区和启动子序列进行突变筛查，并与同时采用相同方法结合构像敏感性凝胶电泳(CSGE)对100个正常对照者的VMD2基因筛查结果进行比较。 结果 Best病家系10个成员中，9人VMD2基因外显子2第223位碱基C-T颠换，其中6人通过眼底和眼电生理检查证实为Best病患者，2人为该突变的纯合子；另外有3个年轻成员虽然携带VMD2基因突变, 临床上仅表现为眼电图的异常。在正常对照者中没有发现上述突变。 结论 Best病家系中VMD2表现型与基因型密切相关，VMD2基因突变是该家系的致病原因。VMD2基因突变筛查可用于Best病的诊断和遗传咨询。 (中华眼底病杂志, 2006, 22: 86-89)

Analysis of the gene mutation of vitelline macular dystrophy in a family with Best disease

Objective To analyze the relationship between genotype and phenotype of vitelline macular dystrophia (VMD2) gene in a family with Best disease, and to provide the theoretical basis for gene diagnosis of Best disease. Methods Mutation in the coding regions and the promotor sequence of VMD2 gene from 10 members in a family with Best disease were screened by polymerase chain reaction (PCR) and direct DNA sequencing, and combined with a conformation sensitive gel electrophoresis (CSGE) approach, VMD2 gene screening was performed on 100 normal control individuals. Results In the 10 members, T→C nucleotide change at the 223 base of exon 3 was detected in 9, including 6 with Best disease who was confirmed by ophthalmoscopy and electrophysiological examination in whom 2 were affirmed as having homozygote of this mutation. Other 3 young family members with VMD2 gene mutation only had abnormal electro-oculogram manifestations. Above mutation was not detected in the normal control individuals. Conclusions The phenotype and genotype of VMD2 in the family with Best disease is highly correlated. Mutation in VMD2 gene is the nosogenesis in this family. Mutation screening of VMD2 gene can be used for genic diagnosis and genetic consultation of Best disease. (Chin J Ocul Fundus Dis, 2006, 22: 86-89)