Liu Zeyuan, Wang He, He Xiaoli, Tao Dan, Li Li
Department of Ophthalmology, Kunming Children's Hospital, No. 288, Qianxing Road, Xishan District, Kunming 650228, China.
Department of Ophthalmology, Kunming Children's Hospital, Yunnan Institute of Pediatrics, Yunnan Province Clinical Research Center for Children's Health and Disease, Yunnan Key Laboratory of Children's Major Disease Research, No. 288, Qianxing Road, Xishan District, Kunming 650228, China.
Open Life Sci. 2023 Jan 16;18(1):20220532. doi: 10.1515/biol-2022-0532. eCollection 2023.
Little is known about the genetic background of pigmented paravenous retinochoroidal atrophy (PPRCA) due to rarity of patients. In this study, we identified two pathogenic variants in in a 2-year-old boy with PPRCA screened by whole-exome sequencing (WES). The patient presented to our department with photophobia for 17 months, and then he underwent fundus photography and fluorescein fundus angiography. Genomic DNA was extracted from peripheral blood of the proband and the parents. Trio-WES strategy was utilized to identify the causal variants from the proband and the parents, followed by validation based on Sanger sequencing. The patient was finally diagnosed with PPRCA after differential diagnosis. Two heterozygous pathogenic variants were detected by WES according to the American college of medical genetics and genomics guidelines, including NM_020366.4: c.2592T > G: p.Y864* and NM_020366.4: c.154C > T: p.R52* in located in exon 17 and exon 3, leading to termination codon, respectively. This is the first study reporting pathogenic variants within as causal for PPRCA.
由于患者稀少，关于色素性静脉旁视网膜脉络膜萎缩（PPRCA）的遗传背景知之甚少。在本研究中，我们通过全外显子组测序（WES）在一名患有PPRCA的2岁男孩中鉴定出两个致病变异。该患者因畏光17个月前来我科就诊，随后接受了眼底照相和荧光素眼底血管造影检查。从先证者及其父母的外周血中提取基因组DNA。采用三联体WES策略从先证者及其父母中鉴定致病变异，随后基于Sanger测序进行验证。经过鉴别诊断，该患者最终被诊断为PPRCA。根据美国医学遗传学与基因组学学会的指南，通过WES检测到两个杂合致病变异，分别为位于第17外显子的NM_020366.4: c.2592T > G: p.Y864和位于第3外显子的NM_020366.4: c.154C > T: p.R52，均导致终止密码子。这是首次报道 内的致病变异作为PPRCA病因的研究。
