Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, No.1 Dongjiaominxiang, Beijing 100730, China.
Ophthalmic Molecular Genetics Section, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Rockville, MD 20892, USA.
Genes (Basel). 2024 Sep 11;15(9):1192. doi: 10.3390/genes15091192.
To delineate the genotype and phenotype of RH in a Chinese cohort. A group of 51 Chinese probands with RH across 76 eyes was assembled and underwent complete retinal imaging examinations. Sanger sequencing and universal primer quantitative fluorescent multiplex-polymerase chain reaction (UPQFM-PCR) were employed for mutation detection in the coding region of the Von Hippel-Lindal () gene. For frequency calculation, our series was combined with three large cohorts of East Asian descent through a literature review. The Von Hippel-Lindal (VHL) syndrome was excluded in fifteen patients (median age: 32.00 years) with unilateral solitary RH. Thirty-six patients of younger ages (median: 22.00 years, = 0.008, Mann-Whitney test) conformed to the diagnostic criteria of the VHL syndrome, and thirty-four patients were genetically confirmed. There were four novel variants identified in the gene. Codons 167, 161 and 86 exhibited a mutation occurrence of more than 5% after pooling with literature data, and the large genomic deletion demonstrated a frequency of 17.65%. The RHs were classified as "extrapapillary", "juxtapapillary" and "mixed" types in 53, 7 and 5 eyes, respectively. Almost all extrapapillary RH lesions were found in the peripheral retina. Hemangioblastomas in the central nervous system (CNS) were observed in 25 out of 31 kindreds (80.65%) with full systemic evaluation data. VHL-associated RH might exhibit earlier onset than non-VHL RH. Large genomic deletions were observed at a notably high frequency in the Chinese series with VHL-associated RH, which might be associated with East Asian ethnicity background. RH could potentially serve as an early indicator of CNS hemangioblastoma.
为了描绘中国人群中 RH 的基因型和表型。我们收集了一组 51 例 RH 患者（76 只眼），并对他们进行了全面的视网膜成像检查。采用 Sanger 测序和通用引物定量荧光多重聚合酶链反应（UPQFM-PCR）对 Von Hippel-Lindal （VHL）基因编码区的突变进行检测。为了计算频率，我们通过文献回顾将我们的系列与三个东亚大型队列进行了组合。在 15 例（中位年龄：32.00 岁）单侧孤立性 RH 患者中排除了 VHL 综合征。36 例年龄较小的患者（中位年龄：22.00 岁，=0.008，Mann-Whitney 检验）符合 VHL 综合征的诊断标准，其中 34 例患者经基因检测证实。在 基因中发现了四个新的变异。将文献数据汇总后，密码子 167、161 和 86 的突变发生率超过 5%，大片段缺失的频率为 17.65%。将 RH 分为“视网膜下型”、“视网膜旁型”和“混合型”，分别为 53、7 和 5 只眼。几乎所有视网膜下型 RH 病变均位于周边视网膜。在有完整系统评估数据的 31 个家系中，25 个家系（80.65%）发现中枢神经系统（CNS）中的血管母细胞瘤。VHL 相关的 RH 发病年龄可能早于非 VHL RH。在中国 VHL 相关 RH 系列中观察到大片段缺失的频率明显较高，这可能与东亚种族背景有关。RH 可能是 CNS 血管母细胞瘤的早期指标。
