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.

中文翻译：

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DYSF 中的空变异导致更早的症状发作

我们调查了韩国dysferlin病患者的临床、实验室和遗传谱，以阐明其基因型-表型相关性。我们回顾性地审查了来自 96 个无关家族的 101 名患者，这些患者具有DYSF 的致病性变异。最常见的初始表型是 50 名患者的三好肌病。检查和症状出现时的中位年龄分别为 23 [四分位距 (IQR)：18-30] 和 36 岁 [IQR：27-48]。我们观察到 38 个变体，包括 9 个新变体。四变体（c.2494C> T，c.1284 + 2 T> C，c.663 + 1G> C和c.2997G> T）在DYSF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，我们比较了无效/无效（N/N；n = 55）和无效/错义变异（N/M；n = 35）患者之间的临床表型。N/N 组的症状发作年龄（中位数：20 岁 [IQR：17-25]）比 N/M 组（中位数：29 岁 [IQR：23-35]，p  < .001）。N/N 组（中位数：80 [IQR：56-92]）下肢的总手动肌肉测试分数低于 N/M 组（中位数：89 [IQR：78-98]，p = . 013)。我们的研究首次报告了DYSF中的空变异比错义变异导致更早的症状发作。