一个家族性显性玻璃膜疣家系的临床表型及分子遗传学分析

Molecular genetic analysis and clinical phenotype of a pedigree with familial dominant drusen

目的 探讨1个家族性显性玻璃膜疣家系的EFEMP1基因突变及其临床表型.方法 通过眼底照相、眼底荧光造影、光学相干断层成像等检查,研究一个家族性显性玻璃膜疣家系的临床特点,并对该家系的患者及正常对照进行分子遗传学分析,应用聚合酶链反应扩增EFEMP1基因的所有编码外显子,并将PCR产物进行直接测序,将测序结果与野生型序列进行比对.同时,对家系中出现脉络膜新生血管及视网膜前出血的先证者行玻璃体腔注射抗血管内皮生长因子（anti-vascular endothelial growth factor,VEGF）.结果 该家系中的两例患者EFEMP1基因第10外显子发生了C＞T（R345W）杂合突变,而在该家系的健康个体及100名健康人对照中未发现相同的突变.玻璃体腔注射抗VEGF药物的患者术后随访,视力明显改善,眼底稳定.结论 该家系中EFEMP1基因的R345W突变导致了家族性显性玻璃膜疣.玻璃体腔抗VEGF药物对于治疗该疾病并发的脉络膜新生血管有良好的效果.

Objective To analyze clinical features and mutations of EFEMP1 gene in a Chinese pedigree with familial dominant drusen.Method Clinical features of the pedigree were studied with fundus photography,fundus fluorescein angiography and optical coherence tomography.Molecular genetic analysis was performed on the patients and unaffected individuals from the family.All coding exons of the EFEMP1 gene were amplified by polymerase chain reaction （PCR） and sequenced.The results were compared with wild-type sequences from NCBI.The proband who had suffered from choroidal neovascularization and preretinal hemorrhage received an intravitreal injection of an anti-vascular endothelial growth factor （VEGF） preparation.Results A heterozygous mutation C〉T （R345W） was identified in exon 10 of the EFEMP1 gene in two affected individuals from the family.The same mutation was not detected in unaffected family members and 100 healthy individuals.Postoperative follow-up of the patient receiving intravitreal injection of anti-VEGF drug showed that visual acuity was improved and fundus appeared to be stable.Conclusion The R345W mutation in EFEMP1 is responsible for the dominant drusen in this family.Intravitreal injection of anti-VEGF drug is a promising treatment for the improvement in vision.