中心晕轮状黄斑营养障碍家系的临床研究和致病基因分析

A Chinese family with central areolar macular dystrophy:clinical and genetic study

目的报道一个少见的中国人中心晕轮状黄斑营养障碍家系,通过候选基因突变分析探讨该家系发病的分子遗传学基础。设计病例系列和突变分析。研究对象中心晕轮状黄斑营养障碍一家系。方法43位家庭成员接受家系调查和临床检查。应用聚合酶链反应(PCR)和DNA序列测定技术对候选基因GUCAlA、RDS和ELOVLA全部外显子和邻近内含子进行检测。主要指标临床特征和基因序列测定。结果家庭成员连续三代发病,共发现患者7人,男女共患,患者双眼发病,病变局限于后极部,呈进行性发展。早期患者视力正常.黄斑区轻度色素变动,随病情进展出现黄斑萎缩。视网膜电图显示视锥细胞功能正常或轻度受损。GUCAIA、RDS和ELOVIA基因的全部外显子和邻近内含子未检出致病性突变。3名患者和3名正常人在RDS基因第一外显子出现杂合或纯合558C>T(Val106Val)多态性改变。结论该家系患者呈常染色体显性遗传。临床表现符合中心晕轮状黄斑营养障碍的基本特征,临床表型与GUCAIA、RDS和ELOVLA基因编码序列无关。

Objective To report a large Chinese family with central areolar macular dystrophy and to identify its genetic entity by mutation analysis of candidate genes. Design Case series and mutation analysis. Participants A family with central areolar macular dystrophy. Method Forty-three individuals in the family were investigated. Genomic DNA was extracted from leukocytes of peripheral blood of the family members. All exons and adjacent introns of GUCA1A, RDS and ELOVL4 genes were amplified by polymerase chain reaction （PCR） and directly sequenced. Main Outcome Measures Clinical features and sequence analysis. Result Seven individuals with central areolar macular dystrophy were demonstrated in the family in three continuous generations, affecting both males and females. The macular appearance varied from relatively normal-appearing fundus to central geographic atrophy. Peripheral retina was normal in all affected individuals. Fluorescein angiography showed a bull＇s eye-like hyperfluorescence in the macula in the early stage and a transmission window defect intermingled with a hypofluorescence in the advanced stage. Electroretinography shows normal or mild reduction in the photopic amplitude. No mutations were detected in all exons and adjacent introns of GUCA1A, RDS and ELOVL4 genes. However, we found a non-pathogenic polymorphism, 558C〉T （Vall06Val）, in exon 1 of RDS. Conclusion Central areolar macular dystrophy is shown in this family and GUCA1A, RDS and ELOVL4 genes are excluded to be responsible for the disease.