ABCA4基因突变与3个不同遗传性视网膜疾病家系临床表型的研究

ABCA4 mutations and phenotype of different hereditary retinopathies in 3 pedigrees

目的研究分析ABCA4基因所致的不同类型遗传性视网膜疾病的基因型和临床表型关系。方法回顾性研究。从2016年1至9月在宁夏眼科医院就诊的遗传性视网膜疾病患者中，选择经Agilent液相捕获技术确定携带ABCA4基因突变位点的家系3个，完善相关病史资料采集，同时对家系患者及其家系成员进行详细眼科检查，包括裸眼视力、最佳矫正视力、眼底检查、相干光断层扫描、眼底荧光造影检查和视觉电生理检查，分析临床表型和基因型之间的关系。结果3个家系均为常染色体隐性遗传家系，3个家系在ABCA4基因上共检测到致病性突变位点4个，其中1个视椎视杆细胞营养不良家系和1个视网膜色素变性（RP）家系各携带1个纯和移码突变，1个Stargardt病家系携带2个杂合突变，3个家系的患者发病年龄均小于10岁，就诊时最佳矫正视力均低于0．1，黄斑OCT提示不同程度的黄斑区萎缩，视觉电生理改变从完全正常到视椎视杆细胞功能严重下降不一。结论携带ABCA4基因突变的遗传性视网膜变性疾病的患者具有发病年龄小，病程进展快，视力损伤严重等特点，二代测序技术在遗传性视网膜疾病的诊断方面具有快速、高效等优点。

Objective To analyze the relationship between genotype and phenotype of different types of hereditary retinopahty caused by ABCA4 gene. Method Three （3） pedigrees that carried mutations on ABCA4 gene as determined through the second generation sequencing technology were selected from the patients diagnosed with hereditary retina/disease in Ningxia Eye Hospital between Januaryand September 2016. The clinical features of patients and other family members of them were collected and analyzed with complete ophthalmic examinations including visual acuity, best corrected visual acuity, fundus examination, maeular OCT, fundus fluorescein angiography and electroretinogram （ERG）. The relationship between genotype and phenotype was analyzed. Results All the 3 pedigrees were autosomal recessive families. Four mutations on ABCA4 gene were detected, the CRD pedigree and the RP pedigress carried a homozygous frameshift mutation respectively. The Stargardt pedigree carried two heterozygous mutations. The onset age of the patients were less than 10 years. The best corrected visual acuity was lower than 0.1 and the maeular OCT indicated different levels of macular area atrophy, and the visual electrophysiological changes varied from completely normal to significantly reduced visual stem cell function in different cases. Conclusions The patients with hereditary retinal disease that carried ABCA4 gene mutations were featured with characteristics of early onset age, rapid progress and severe visual impairment. The second generation sequencing technique has the advantages of rapidness and high efficiency in the diagnosis of hereditary retinal disease.