Department of Neurology, Rehabilitation Institute of Neuromuscular Disease, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Department of Biochemistry, College of Medicine, Dong-A University, Busan, South Korea.
Clin Genet. 2021 Mar;99(3):396-406. doi: 10.1111/cge.13887.
We investigated the clinical, laboratory, and genetic spectra in Korean patients with dysferlinopathy to clarify its genotype-phenotype correlation. We retrospectively reviewed 101 patients from 96 unrelated families with pathogenic variants of DYSF. The most common initial phenotype was Miyoshi myopathy in 50 patients. Median ages at examination and symptom onset were 23 [interquartile range (IQR): 18-30] and 36 years [IQR: 27-48], respectively. We observed 38 variants, including nine novel variants. Four variants (c.2494C > T, c.1284 + 2 T > C, c.663 + 1G > C, and c.2997G > T) in DYSF accounted for 62% of total allele frequencies of pathogenic variants. To analyze the genotype-phenotype correlation, we compared the clinical phenotype between patients with null/null (N/N; n = 55) and null/missense variants (N/M; n = 35). The N/N group had an earlier symptom onset age (median: 20 years [IQR: 17-25]) than the N/M group (median: 29 years [IQR: 23-35], p < .001). Total manual muscle testing scores in lower extremities were lower in the N/N group (median: 80 [IQR: 56-92]) than in the N/M group (median: 89 [IQR: 78-98], p = .013). Our study is the first to report that null variants in DYSF result in an earlier symptom onset than missense variants.
我们调查了韩国肌营养不良症患者的临床、实验室和遗传谱，以阐明其基因型-表型相关性。我们回顾性分析了 96 个无关家庭的 101 名携带 DYSF 致病变异的患者。最常见的初始表型是 50 名患者的 Miyoshi 肌病。检查和症状发作的中位年龄分别为 23 [四分位距 (IQR)：18-30] 和 36 岁 [IQR：27-48]。我们观察到 38 种变异，包括 9 种新变异。DYSF 中的 4 种变异（c.2494C > T、c.1284 + 2 T > C、c.663 + 1G > C 和 c.2997G > T）占致病变异总等位基因频率的 62%。为了分析基因型-表型相关性，我们比较了 N/N（n = 55）和 N/M（n = 35）患者之间的临床表型。N/N 组的症状发作年龄较早（中位数：20 岁 [IQR：17-25]），N/M 组的症状发作年龄较晚（中位数：29 岁 [IQR：23-35]，p <.001）。N/N 组下肢总手动肌肉测试评分较低（中位数：80 [IQR：56-92]），N/M 组评分较高（中位数：89 [IQR：78-98]，p =.013）。我们的研究首次报道 DYSF 中的无义变异导致的症状发作早于错义变异。
