目的:莱伯先天性黑蒙(LCA)是一组早发性视网膜退行性疾病,导致儿童失明。本研究旨在描述一组LCA患者的临床和遗传特征,并研究LCA患者的视网膜血管特征。
方法:52名LCA儿童被纳入研究。所有患者都接受了详细的眼部检查。视网膜电图(ERG)用于评估视网膜功能。光学相干断层扫描(OCT)用于评估那些能够很好地合作的患者的视网膜结构变化。进行基于面板的下一代测序以鉴定与LCA相关的基因中的致病变体。使用具有人工智能(AI)技术的EVisionAI筛查系统测量视网膜血管的直径。使用超声多普勒评估血流动力学参数,包括峰值收缩期速度(PSV),电阻指数(RI),和搏动指数(PI),在眼科,视网膜中央,后睫状,颈动脉,12名年龄在3至14岁之间的患者的颈内动脉以及颈外动脉。
结果:我们从RPGRIP1,CEP290,GUCY2D,LCA5,AIPL1,CRB1,RPE65,CRX,RDH12和TULP1,包括52名受影响的LCA儿童中的29种新颖和36种先前报道的变体,RPGRIP1的检出率最高(26.9%)。LCA患者眼底外观多样,范围从正常到严重的周围或中央视网膜病变。在12例具有不同基因变异的患者中评估了视网膜血管系统,显示狭窄的动脉,平均直径为43.6±3.8μm,而正常对照组为51.7±2.6μm(P<0.001,n=12)。同时,他们的血液动力学参数在眼动脉(OA)中也发生了变化,与正常对照组相比,PSV降低(P=0.0132,n=12),PI略有增加(P=0.0488,n=12)。然而,其他血管的血流动力学参数没有显著变化.
结论:预测LCA患者眼球的血液供应减少,可能是由于感光细胞变性。新鉴定的变体将扩展LCA相关基因中的变体谱,并可用于研究LCA的分子机制。
OBJECTIVE: Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders, resulting in blindness in children. This study aimed to describe the clinical and genetic characteristics of a cohort of patients with LCA and to investigate the retinal vascular characteristics in LCA patients.
METHODS: Fifty-two children with LCA were included in the study. All patients underwent detailed ocular examinations. Electroretinography (ERG) was used to evaluate the retinal function. Optical coherence tomography (OCT) was used to assess the structure change of the retina for those patients who were able to cooperate very well. Panel-based next-generation sequencing was performed to identify pathogenic variants in genes associated with LCA. Diameters of the retinal vessels were measured using the EVision AI screening system with an artificial intelligence (AI) technique. An ultrasound Doppler was used to evaluate hemodynamic parameters, including peak systolic velocity (PSV), resistive index (RI), and pulsatility index (PI), in the ophthalmic, central retinal, posterior ciliary, carotid, and internal carotid as well as external carotid arteries in 12 patients aged from 3 to 14 years.
RESULTS: We detected 75 pathogenic variants from ten genes of RPGRIP1, CEP290, GUCY2D, LCA5, AIPL1, CRB1, RPE65, CRX, RDH12, and TULP1, including 29 novel and 36 previously reported variants in 52 affected children with LCA, with the highest detective rate in RPGRIP1 (26.9%). Fundus appearance is diverse in patients with LCA, ranging from normal to severe peripheral or central retinopathy. Retinal vasculature was evaluated in 12 patients with different gene variants, showing narrowed arteries with an average diameter of 43.6 ± 3.8 μm compared to that of 51.7 ± 2.6 μm in the normal controls (P < 0.001, n = 12). Meanwhile, their hemodynamic parameters were changed as well in the ophthalmic artery (OA), with a decreased PSV (P = 0.0132, n = 12) and slightly increased PI (P = 0.0488, n = 12) compared to the normal controls. However, the hemodynamic parameters did not change significantly in the other vessels.
CONCLUSIONS: Blood supply to the eyeball is predicted to be reduced in patients with LCA, presumably due to photoreceptor cell degeneration. The novel identified variants will expand the spectrum of variants in LCA-related genes and be useful for studying the molecular mechanisms of LCA.