Chair and Department of General and Pediatric Ophthalmology, Medical University of Lublin, 20-059 Lublin, Poland.
Department of Forensic Medicine, Medical University of Lublin, 20-059 Lublin, Poland.
Genes (Basel). 2023 Oct 17;14(10):1950. doi: 10.3390/genes14101950.
The goal of the study was to explore the spectrum of pathogenic variants in the RPGR gene in a group of male Polish patients with a retinitis pigmentosa (RP) phenotype. A total of 45 male index patients, including twins, being members of 44 families, were screened for pathogenic variants in the RPGR gene via the direct sequencing of PCR-amplified genomic DNA and underwent a comprehensive ophthalmological examination in one center located in Poland. A total of two pathogenic and five likely pathogenic variants in eight patients (18%) were detected in the studied cohort. Of these, five variants were novel, and five disease-causing variants (71%) were identified within the ORF15 mutational hotspot of the RPGR gene. The median age of onset of the disease was 10 years (range 6-14 years), the median age during the examination was 30 years (range 20-47 years), and the median visual acuity was 0.4 (range 0.01-0.7). The majority of patients had middle constriction of the visual field and thinning of the central foveal thickness. Dizygotic twins bearing the same hemizygous mutation showed a different retinal phenotype in regard to the severity of the symptoms. This is the first RPGR mutation screening in Poland showing a prevalence of 18% of RPGR pathogenic mutations and likely pathogenic variants in the studied cohort of male patients with an RP phenotype.
本研究旨在探索一组波兰男性视网膜色素变性(RP)表型患者中 RPGR 基因的致病变异谱。通过对 45 名男性索引患者(包括双胞胎)的 RPGR 基因进行 PCR 扩增基因组 DNA 的直接测序,对来自 44 个家族的 45 名男性索引患者进行了筛查,并在波兰的一个中心进行了全面的眼科检查。在研究队列中,共在 8 名患者(18%)中检测到两种致病性和五种可能致病性变异。其中,有五种变异是新发现的,五种致病变异(71%)位于 RPGR 基因的 ORF15 突变热点内。疾病发病的中位年龄为 10 岁(范围 6-14 岁),检查时的中位年龄为 30 岁(范围 20-47 岁),中位视力为 0.4(范围 0.01-0.7)。大多数患者的视野中间有缩窄,中央黄斑厚度变薄。携带相同半合子突变的异卵双胞胎在视网膜表型的严重程度方面表现出不同的表现。这是波兰首次进行 RPGR 突变筛查,在研究队列中,18%的男性 RP 表型患者存在 RPGR 致病性突变和可能的致病性变异。