Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Graefes Arch Clin Exp Ophthalmol. 2024 Jan;262(1):337-351. doi: 10.1007/s00417-023-06178-y. Epub 2023 Aug 16.
To investigate the clinical and genetic characteristics for a large cohort of Chinese patients with Bietti crystalline retinopathy (BCR).
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.
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).
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.
研究中国大样本 Bietti 结晶状视网膜病变（BCR）患者的临床和遗传特征。
共招募了 175 个家系的 208 名中国 BCR 患者。进行了全面的临床评估和基因分析。通过统计分析评估了基因型-表型相关性。
患者的中位年龄为 37 岁（范围，20-76 岁）。中位最佳矫正视力（BCVA）为 0.8 LogMAR 单位（范围，2.8 至-0.12）。40 岁以上患者的 BCVA 明显下降（P<0.001）。观察到两种临床类型：周边型（type P）和中央型（type C）。type C 患者的中央视力更差，但视网膜功能保存得更好（P<0.05）。分子筛查在 98.3%（172/175）的家系中检测到双等位基因 CYP4V2 致病性变异，包括 19 个新变异。最常见的致病性变异是 c.802-8_810del17insGC，等位基因频率为 55.7%（195/350），其次是 c.992A>C（28/350，8%）和 c.1091-2A>G（23/350，6.6%）。BCR 患者携带一个 c.802-8_810del17insGC 和一个截断变异（IVS6-8/Tru），其 BCVA>1.3 LogMAR 单位（Snellen 等效视力<20/400）的年龄小于纯合 c.802-8_810del17insGC 变异（homo IVS6-8）的患者（P=0.031）。
BCR 患者在 40 岁之前保持相对较好的视力。观察到两种不同的 BCR 临床类型。携带 IVS6-8/Tru 的 BCR 患者视力下降比携带 homo IVS6-8 的患者更早。我们的发现增强了对 BCR 的认识，并有助于基因治疗患者的选择。
