摘要目的:对1例早发视网膜色素变性(RP)患者进行遗传学分析。方法:选取2022年3月10日于四川大学华西医院就诊的1例患者作为研究对象。通过全外显子组测序(WES)对患者及其父母进行变异筛查，对候选变异进行Sanger测序家系验证以及致病性分析。结果:患者双眼视野严重损失，眼底检查显示骨针状色素沉着、视网膜小动脉衰减和视盘苍白。WES检测显示患者 CRB1基因存在c.2969T>C(p.Leu990Ser)和c.1816T>C(p.Cys606Arg)复合杂合错义变异，分别遗传自其父母。 CRB1基因c.1816T>C(p.Cys606Arg)纯合变异既往曾在一个视网膜色素变性家系中被检出，而c.2969T>C(p.Leu990Ser)变异则未见报道。根据美国医学遗传学与基因组学学会(ACMG)相关指南，二者均被评级为可能致病变异。 结论:CRB1基因c.2969T>C(p.Leu990Ser)和c.1816T>C(p.Cys606Arg)复合杂合变异可能是本研究患者发生早发性视网膜色素变性的遗传学病因。上述发现拓展了 CRB1基因的变异谱。

abstractsObjective:To explore the genetic basis for a patient with early-onset retinitis pigmentosa (RP).Methods:A patient who had presented at the West China Hospital of Sichuan University on March 10, 2022 was selected as the study subject. The patient and his parents were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and in silico analysis. Results:The patient has featured substantial loss of binocular vision field. Funduscopy revealed characteristic bone spicule-type pigment deposits, as well as attenuated retinal arterioles and pale-appearing optic discs. WES revealed that he has harbored compound missense variants of a RP-associated CRB1 gene, including c. 2969T>C (p.Leu990Ser) and c. 1816T>C (p.Cys606Arg), which were respectively inherited from his father and mother. Homozygous c. 1816T>C (p.Cys606Arg) variant has been identified among RP patients, whilst the c. 2969T>C (p.Leu990Ser) variant was unreported previously. Both variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:The novel compound heterozygous variants of the CRB1 gene probably underlay the early-onset RP in this patient. Above finding has enriched the mutational spectrum of the CRB1 gene.