Liu Nanxin 1,3 , Mahri Hommodova 1 , Ren Yue 2 , Hong Yanfen 1 , Xiong Ming 1 , Rong Jia 2 , Liu Shu 2 , Wang Di 2 , Chen Zijie 1 , Zhu Yihua 3 , Liu Xuyang 1 , Pang Jijing 1,2
  • 1. Xiamen Eye Center of Xiamen University, Xiamen 361001, China;
  • 2. Shenyang He Eye Specialist Hospital, Shenyang 110000, China;
  • 3. Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China;
Liu Xuyang, Email: xliu1213@126.com
X-linked retinitis pigmentosa; RP2 gene; RPGR gene; Whole-exome sequencing; Genovariation
10.3760/cma.j.cn511434-20250516-00217
Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables References Cited by

Objective To identify and observe the pathogenic gene variants and clinical phenotypes of two Han Chinese families with X-linked retinitis pigmentosa (XLRP). Methods A family-based investigation study. Two unrelated Han Chinese XLRP families, whose probands were diagnosed via genetic testing after clinical visits at Xiamen Eye Center in 2019 and 2025 respectively, were enrolled in this study, including 7 and 51 family members correspondingly. Detailed family history, marital-reproductive history and systemic disease history were collected. Ophthalmic examinations including best-corrected visual acuity (BCVA), fundus color photography, optical coherence tomography (OCT) and full-field electroretinogram (ERG) were performed. Peripheral venous blood samples were collected from participants for whole-genomic DNA extraction. Whole-exome sequencing was applied to screen pathogenic variants, and Sanger sequencing was used for familial validation of candidate variant sites. Pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines, together with online bioinformatic tools including SIFT, Mutation Taster, CADD and RDDC. Results The proband of family 1 (F1-Ⅱ3), a 33-year-old male, presented with night blindness since childhood. His BCVA was 0.04 in the right eye and 0.05 in the left eye. Multifunctional bone-spicule-like pigment depositions were observed in the temporal retina of both eyes. OCT revealed focal thickening of the retinal pigment epithelium and loss of ellipsoid zone reflectivity. No stable rod- or cone-derived responses were detected on full-field ERG. This family was affected for three consecutive generations, showing X-linked inheritance characteristics. The proband carried a semi-synonymous missense variant of the RP2 gene, c.353G>C (p.Arg118Pro, M1). The proband’s mother and eldest daughter carried a heterozygous variant of M1, while the father and second son were wild-type. The proband of family 2 (F2-Ⅳ4) was a 6-year-old female. She had poor vision since childhood. At 8 months of age, she was found to have high astigmatism in both eyes during a physical examination. From the age of 4, she received amblyopia training but her vision did not show significant improvement. The full-field ERG showed decreased a-wave amplitude during dark adaptation and normal latency, decreased b-wave amplitude with delayed latency, and decreased a and b-wave amplitudes during bright adaptation with normal latency in all. This family had multiple members with poor vision since childhood and relying on refractive correction, with the disease affecting three consecutive generations. Male patients only passed the pathogenic gene to their daughters, which conforms to the X-linked dominant inheritance pattern. The proband carried a heterozygous small deletion variant of the RPGR gene, c.2405_2406del (p.Glu802Glyfs*32, M2). The father carried a semi-heterozygous small deletion variant of M2, while the mother and younger brother were wild-type. This variant co-segregated in all affected males, and some women carrying this variant also exhibited the corresponding clinical phenotype. Bioinformatics analysis showed that the M1 and M2 variants were predicted to be harmful by CADD, RDDC, SIFT, and Mutation Taster; M1 was not included in the gnomAD database and was a new rare variant; M2 was a known variant in the ClinVar database. According to the ACMG guidelines, both M1 and M2 were rated as likely pathogenic variants.Conclusions The hemizygous missense variant M1 in RP2 and the hemizygous small deletion variant M2 in RPGR are likely pathogenic variants for family 1 and family 2, respectively. M1 represents a previously unreported novel variant.

Citation： Liu Nanxin, Mahri Hommodova, Ren Yue, Hong Yanfen, Xiong Ming, Rong Jia, Liu Shu, Wang Di, Chen Zijie, Zhu Yihua, Liu Xuyang, Pang Jijing. Clinical phenotype and genetic characteristics analysis of two Chinese Han X-Linked retinitis pigmentosa pedigrees. Chinese Journal of Ocular Fundus Diseases, 2026, 42(9): 764-771. doi: 10.3760/cma.j.cn511434-20250516-00217 Copy

Copyright ? the editorial department of Chinese Journal of Ocular Fundus Diseases of West China Medical Publisher. All rights reserved

  • Previous Article

    Investigation of the correlation between ABCC6 gene variation and clinical phenotype of pseudoxanthoma elasticum within a family

  • Next Article

    Analysis of clinical manifestations and genetic characteristics in families with ocular albinism