Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
Eye (Lond). 2023 Nov;37(16):3398-3405. doi: 10.1038/s41433-023-02516-w. Epub 2023 Apr 8.
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.
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.
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.
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.
Bardet-Biedl 综合征（BBS）是一种罕见的多系统纤毛病。本研究旨在描述携带双等位基因 BBS 基因突变的中国患者的临床和遗传特征。
我们招募了 31 个无关家系中携带双等位基因 BBS 基因突变的 34 名患者。所有患者均接受了眼科和系统评估以及全面的分子遗传学分析。最终，有 14 名患者进行了随访。
我们在 10 个 BBS 基因中发现了 47 个致病变异，其中 33 个是新的。27 个家系的 28 名患者和 6 名患者被诊断为 BBS 和非综合征性视网膜色素变性（RP）。在患者中最常见的两个基因是 BBS2 和 BBS4，占先证者的 51.8%。患者表现出临床异质性，从具有所有六个主要临床成分的患者到患有非综合征性 RP 的患者。常见的成分是视网膜营养不良、多指畸形和肥胖，频率为 78.6%至 100%，而肾异常频率仅为 7.1%。患者表现出早期和严重的视力缺陷和视网膜变性。携带 BBS2 双等位基因错义变异的患者临床症状较少，视力损害较轻。携带 BBS10 变异的患者倾向于患有 Cone 变性。
本研究确定了中国患者突变基因谱，并建立了每个 BBS 基因变异频率的配置。总体而言，我们的患者表现出早期和严重的视力缺陷和视网膜变性。因此，遗传分析对于这些患者的诊断、遗传咨询和未来的基因治疗至关重要。
