Abstract
Purpose
Bardet-Biedl syndrome (BBS) is a rare multisystem ciliopathy. The aim of this study was to describe the clinical and genetic features of a cohort of Chinese patients carrying biallelic BBS gene variants.
Methods
We recruited 34 patients from 31 unrelated pedigrees who carried biallelic pathogenic variants in BBS genes. All patients underwent ophthalmic and systematic evaluations, as well as comprehensive molecular genetic analyses. Ultimately, 14 patients were followed up over time.
Results
We identified 47 diseasing-causing variants in 10 BBS genes; 33 were novel. Diagnosis of BBS and non-syndromic retinitis pigmentosa (RP) were established in 28 patients from 27 pedigrees and 6 patients, respectively. The two most prevalent genes in patients with BBS were BBS2 and BBS4, accounting for 51.8% of the probands. The patients exhibited clinical heterogeneity, from patients with all six primary clinical components to patients suffering from non-syndromic RP. The common components were retinal dystrophy, polydactyly, and obesity, with frequencies of 78.6% to 100%, while renal anomaly frequencies were only 7.1%. Patients exhibited early and severe visual defects and retinal degeneration. Patients with biallelic missense variants in BBS2 suffered fewer clinical symptoms and mild visual impairment. Patients with BBS10 variants tended to have cone dystrophy.
Conclusions
Our study defined the mutated gene profiles and established the configuration of the variation frequencies for each BBS gene in Chinese patients. Overall, our patients showed early and severe visual defects and retinal degeneration. Genetic analysis is therefore crucial for diagnosis, genetic counseling, and future gene therapy in these patients.
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Data availability
The datasets generated during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This study was supported by the National Key R&D Program of China (2016YFC0905200). The funding organizations had no role in designing or conducting this research.
Funding
This work was supported by the National Key R&D Program of China, 2016YFC0905200. The funding organization had no role in the design or conduct of this research.
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JZ and YX participated in the study design, acquired the data, and drafted the manuscript. HY, CC, TS, KX, and XZ analyzed the data and aided in interpreting the results. YL designed the current study and revised the manuscript. All authors read and approved the final manuscript.
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Zhong, J., Xie, Y., Ye, H. et al. Phenotypic diversity observed in a Chinese patient cohort with biallelic variants in Bardet-Biedl syndrome genes. Eye 37, 3398–3405 (2023). https://doi.org/10.1038/s41433-023-02516-w
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DOI: https://doi.org/10.1038/s41433-023-02516-w
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