Leber先天性黑矇患者的临床表型及遗传学分析

Clinical features and genetic study of three patients with leber congenital amaurosis

目的对Leber先天性黑矇(leber congenital amaurosis,LCA)患者的临床表型及基因型进行分析,为家系遗传咨询和产前诊断提供依据。方法将2016年6月—8月经临床检查确认为LCA的3例患者及其父母纳入研究,详细收集病史、家族史,患者父母行裂隙灯显微镜、间接检眼镜检查,患者行全身麻醉下RetcamⅡ眼底血管造影检查。采集患者及其家庭成员外周静脉血,提取全基因组DNA,采用全外显子组测序技术对3例LCA患者及其父母进行遗传学诊断及分型,并结合患者的临床特点进行分析。结果 3例LCA患者临床诊断明确,眼底表现各有差异,患者1携带SPATA7纯合突变,c.744(E5)至c.745(E5)插入T, p.249, L>Ffs4,眼底表现为双眼视盘颜色苍白,视盘周围血管闭塞呈"白线"状,视网膜广泛椒盐状色素改变。患者2携带WFS1杂合突变,突变为4号染色体5号外显子c.535G>A,p.A179T,眼底表现为双眼视盘苍白,视网膜血管变细。患者3携带CRB1、RPGRIP1、SPATA7杂合突变,眼底表现为双眼视盘苍白,对称性黄斑色素上皮萎缩,视网膜、脉络膜广泛脱色素及变性。结论 LCA具有遗传异质性与临床表型多样性的特点。

Objective To investigate the genotype and phenotype in patients with leber congenital amaurosis （LCA）, and offer accurate genetic counseling and prenatal diagnosis for those families. Methods Three LCA patients and their parents were recruited for this study and received detailed collection of medical history and family history from March to August 2016. The three patients received fundus fluorescein angiography examination and their parents received slit-lamp microscope and indirect ophthalmoscopy examinations. DNA was extracted from the patients and their family members. Whole-exome sequencing method was used for genetic diagnosis and typing of the three LCA patients and their parents. Results The three patients with different clinical features had a definite clinical diagnosis of LCA. Patient 1 showed pale disc, attenuated vessels aroud the optic disc and the salt-and-pepper appearance of the retina, had the homozygous c.744.745insT （p.249, L〉Ffs4） mutation in SPATAT. Patient 2 showed optic disc pallor and attenuated retinal vessels, had the heterozygous c.535G〉A, p.A179T mutation in WFS1. Patient 3 showed pale disc, atrophic macular and retinal and choroidal degeneration, had the heterozygous mutation in CRBI, RPGRIP1, SPATAZ Conclusion LCA has characteristics of genetic heterogeneity and clinical and phenotypic diversity.