You are here

  • Home
  • Online First
  • Clinical and mutational signatures of CRB1-associated retinopathies: a multicentre study

Article Text

Article menu
Download PDFPDF
Genotype-phenotype correlations
Original research
Clinical and mutational signatures of CRB1-associated retinopathies: a multicentre study
  1. Mo-Ying Wang1,2,3,
  2. Feng-Juan Gao1,2,3,
  3. Yu-Qiao Ju1,2,3,
  4. Lin-Ying Guo4,
  5. Cong Duan5,
  6. Qing Chang1,2,3,
  7. Ting Zhang1,2,3,
  8. Ge-Zhi Xu1,2,3,
  9. Hui Du6,
  10. Yuan Zong1,2,3,
  11. Xin Huang1,2,3
  1. 1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China
  2. 2Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
  3. 3NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shangai, China
  4. 4Department of Radiology, Eye & ENT Hospital, Fudan University, Shanghai, China
  5. 5Yunnan Eye Institute & Key Laboratory of Yunnan Province, Yunnan Eye Disease Clinical Medical Center, Affiliated Hospital of Yunnan University, Yunnan, China
  6. 6School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China
  1. Correspondence to Dr Xin Huang; fd2017huangxin{at}163.com; Dr Yuan Zong; zongyuan326{at}163.com; Dr Hui Du; sdduhui{at}hotmail.com

Abstract

Background To delineate the clinical and mutational signatures of patients with CRB1-associated retinopathies.

Methods This multicentre retrospective cohort study involved 40 patients with CRB1 mutations and 40 age-matched and gender-matched inherited retinal diseases (IRDs). The detailed phenotyping and genotyping characteristics and genotype‒phenotype correlations of the patients were analysed.

Results The mean age of CRB1 cohort was 27.33±14.63 years. Results showed that yellowish geographic macular degeneration (66.67%), small white or yellow dots (65.6%), hyperopia (62.5%), abnormally laminated retina (61.61%), epiretinal membrane (60.6%) and nummular pigment deposits (50%) were the most common signatures in patients with CRB1 mutations. These clinical signatures were notably more prevalent among CRB1 patients than among individuals in other IRD groups (p<0.001). Early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) patients are more likely to present these signatures than retinitis pigmentosa (RP) and macular dystrophy (MD) patients. Furthermore, a significant reduction in central foveal thickness coupled with pronounced thickening of the peripheral retina was observed more distinctly in patients with EOSRD/LCA (p<0.001). The choroidal thickness was not significantly altered compared to the normal controls, but was markedly reduced in the other IRD groups (p<0.001). 55 pathogenic variants were identified, 20 of which were novel. Null mutations were associated with EOSRD/LCA patients, and missense mutations were more prevalent in MD and RP patients.

Conclusions Key clinical and mutational signatures were demonstrated in this study, providing a comprehensive update on CRB1-associated retinopathies that will aid in diagnosis and lay the foundation for future therapeutic studies.

  • inherited retinal disease
  • genotype-phenotype
  • retinal thickness

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. The data that support the findings of this study are available from the corresponding author on reasonable request.

https://doi.org/10.1136/jmg-2024-110289

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    All data relevant to the study are included in the article or uploaded as online supplemental information. The data that support the findings of this study are available from the corresponding author on reasonable request.

    View Full Text

    Footnotes

    • M-YW, F-JG and Y-QJ contributed equally.

    • Correction notice This article has been corrected since it was published online first. The list of affiliations, and one sentence in the Introduction section, have been corrected.

    • Contributors XH, F-JG and YZ conceived and designed the experiments. YZ, F-JG, CD, YJ and M-YW collected the clinical samples. F-JG, YJ and YZ analysed sequencing data. YZ, F-JG, CD, YJ, TZ, M-YW, L-YG, XH and QC recruited patients, performed clinical examination of patients and clinical interpretation. F-JG, YZ, XH, YJ, M-YW and HD analysed and interpreted the data. F-JG drafted and revised the manuscript. All authors read and approved the manuscript. XH is the guarantor.

    • Funding This study is supported by the Shanghai ‘Rising Stars of Medical Talents’ Youth Development Program, the National Natural Science Foundation of China (grants NSFC82101149, 82070975 and 82201204), the Shanghai Science and Technology Commission (grant no. 21ZR1411400) and Shanghai Hospital Development Center Foundation (SHDC12023116).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.