摘要目的:探讨1例 ABCA4基因变异所致Stargardt病患儿的临床特点和基因变异。 方法:选取深圳市眼科医院2020年9月5日至2023年4月3日诊治的1例患儿为研究对象，分析其临床特征。收集患儿的临床资料，对患儿及其父母的外周血样本进行全外显子组测序，对候选变异进行Sanger测序验证与生物信息学分析。本研究经深圳市眼科医院医学伦理委员会批准(批准号：2022KYPJ072)。结果:患儿为10岁男性，表现为双眼裸眼视力0.1，矫正无助，眼底照相显示黄斑区弥漫分布大量黄白色斑点，自发免疫荧光(FAF)显示中心低荧光伴周围环状高荧光，OCT显示中心凹厚度显著变薄(右眼45 μm/左眼50 μm)伴椭圆体带缺失。全外显子组测序及Sanger测序结果显示患儿 ABCA4基因存在c.2384G>T(p.Gly795Val)和c.2903G>A(p.Arg968Glu)复合杂合变异，其父母分别为单杂合携带者(表型正常)，符合常染色体隐性遗传，既往未见报道。根据美国医学遗传学与基因组学学会(ACMG)序列变异解读指南，该2个变异均被评定为可能致病性(PM2_Supporting＋PM3＋PP3＋PP4；PM1＋PM2_Supporting＋PP3＋PP4)。 结论:ABCA4基因复合杂合变异考虑为该Stargardt病1型患儿的遗传学病因。本研究发现扩展了中国人群 ABCA4基因的变异谱，为Stargardt病遗传异质性和基因型-表型相关性的理解提供依据。

abstractsObjective:To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. Methods:A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).Results:The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c. 2384G>T (p.Gly795Val) and c. 2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+ PM3+ PP3+ PP4; PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.