Department of Ophthalmology, Eye, ENT Hospital of Fudan University, Shanghai, 200031, China.
Shanghai Key Laboratory of Visual Impairment, Restoration, Fudan University, Shanghai, 200031, China.
BMC Ophthalmol. 2024 Aug 26;24(1):373. doi: 10.1186/s12886-024-03640-1.
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases. However, it is still not well understand about the relationship between PCDH15 variants and RP.
In this study, we enrolled a Chinese autosomal recessive retinitis pigmentosa (arRP) pedigree and identified the causative gene in the proband by targeted whole exome sequencing (WES). The variants were validated in the family members by Sanger sequencing and co-segregation analysis.
Novel compound heterozygous, Frame shift variants of the PCDH15 gene, NM_001384140.1:c.4368 - 2147_4368-2131del and NM_001384140.1:c exon19:c.2505del: p. T836Lfs*6 were identified in the arRP pedigree, which co-segregated with the clinical RP phenotypes. The PCDH15 protein is highly conserved among species.
This is the first study to identify novel compound heterozygous variants c.4368 - 2147_4368-2131del and c.2505del(p.T836Lfs*6) in the PCDH15 gene which might be disease-causing variants, and extending the variant spectra. All above findings may be contribute to genetic counseling, molecular diagnosis and clinical management of arRP disease.
色素性视网膜炎（RP）是一组异质性遗传性视网膜疾病。然而，PCDH15 变异与 RP 之间的关系仍不清楚。
本研究中，我们招募了一个中国常染色体隐性遗传视网膜炎（arRP）家系，并通过靶向全外显子组测序（WES）在先证者中鉴定出致病基因。通过 Sanger 测序和共分离分析在家族成员中验证了变体。
在 arRP 家系中发现了 PCDH15 基因的新型复合杂合框移变异，NM_001384140.1:c.4368_2147_4368-2131del 和 NM_001384140.1:c exon19:c.2505del：p.T836Lfs*6，与临床 RP 表型共分离。PCDH15 蛋白在物种间高度保守。
这是首次在 PCDH15 基因中发现新型复合杂合变异 c.4368_2147_4368-2131del 和 c.2505del(p.T836Lfs*6)，可能是致病变异，并扩展了变异谱。所有这些发现可能有助于 arRP 疾病的遗传咨询、分子诊断和临床管理。
