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Clinical and genetic characterization of a large cohort of Chinese patients with Bietti crystalline retinopathy

  • Genetics
  • Published:
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Abstract

Purpose

To investigate the clinical and genetic characteristics for a large cohort of Chinese patients with Bietti crystalline retinopathy (BCR).

Methods

A total of 208 Chinese BCR patients from 175 families were recruited. Comprehensive clinical evaluations and genetic analysis were performed. Genotype-phenotype correlations were evaluated through statistical analysis.

Results

The patients’ median age was 37 years (range, 20–76 years). The median best corrected visual acuity (BCVA) was 0.8 LogMAR unit (range, 2.8 to −0.12). A significant decline of BCVA was revealed in patients over 40 years old (P<0.001). Two clinical types were observed: peripheral type (type P) and central type (type C). Significantly more type C patients had a worse central visual acuity, but a more preserved retinal function (P<0.05). Molecular screening detected biallelic CYP4V2 pathogenic variants in 98.3% (172/175) of the families, including 19 novel ones. The most frequent pathogenic variant was c.802-8_810del17insGC, with the allele frequency of 55.7% (195/350), followed by c.992A>C (28/350, 8%) and c.1091-2A>G (23/350, 6.6%). BCR patients with one c.802-8_810del17insGC and one truncating variant (IVS6-8/Tru) had BCVA>1.3 LogMAR unit (Snellen equivalent<20/400) at a younger age than those with homozygous c.802-8_810del17insGC variants (homo IVS6-8) (P=0.031).

Conclusions

BCR patients preserved relatively good vision before 40 years old. Two distinct clinical types of BCR were observed. BCR patients with IVS6-8/Tru had an earlier decline in visual acuity than those with homo IVS6-8. Our findings enhance the knowledge of BCR and will be helpful in patient selection for gene therapy.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors thank the patients who participated in the study.

Funding

This work was supported by National High Level Hospital Clinical Research Funding (2022-PUMCH-B-102) and CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-003), the National Natural Science Foundation of China (81873687).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    Huajin Li, Xing Wei, Shijing Wu, Tian Zhu, Zixi Sun, Hui Li, Xiaoxu Han, Xuan Zou & Ruifang Sui

  2. Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    Fengxia Yao

  3. State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    Xing Wei, Zixi Sun, Xuan Zou, Fengxia Yao & Ruifang Sui

  4. Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China

    Huajin Li

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Contributions

HJL analyzed the data and wrote the manuscript; XW, SJW, TZ, ZXS, and FXY conducted the experiments and analyzed the data; HL, XXH, and XZ performed the clinical examinations. RFS designed and coordinated the study, supervised the research, collected and analyzed data, and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ruifang Sui.

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Ethics approval

This study was approved by the Institutional Review Board of PUMCH and adhered to the tenets of the Declaration of Helsinki. Informed consents were obtained to use the patients’ medical data.

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Informed consents were obtained to publish the patients’ medical data and photographs.

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The authors declare no competing interests.

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Supplementary information

ESM 1

Supplementary Figure 1. Fourteen pseudo-dominant and 2 pseudo-X-linked BCR pedigrees of the present study. (a) Pseudo-dominant BCR pedigrees. (b) Pseudo-X-linked BCR pedigrees. Squares indicate men; circles indicate women; black indicates affected subjects; slash indicates dead subjects; black arrow indicates proband. (PNG 705 kb)

High resolution image (TIF 5009 kb)

ESM 2

Supplementary Figure 2. Fundus photographs(a-c) and OCT(d-f) of 3 BCD patients aged 35(a,d), 28(b,e) and 48(c, f), respectively. Fundus images showed numerous yellow-white crystalline deposits on retina, irregular pigment clumps, progressive atrophy of RPE and choriocapillaris. Crystalline deposits gradually diminished in advanced stage. OCT revealed reduced retinal thickness, discontinued, and finally disappeared ellipsoid zone, progressive RPE and choroid atrophy. (PNG 7592 kb)

High resolution image (TIF 10796 kb)

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Li, H., Wei, X., Wu, S. et al. Clinical and genetic characterization of a large cohort of Chinese patients with Bietti crystalline retinopathy. Graefes Arch Clin Exp Ophthalmol 262, 337–351 (2024). https://doi.org/10.1007/s00417-023-06178-y

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