【摘要】 目的 探讨检测4q D4Z4末端甲基化水平在肩腓综合征(SPMD)诊断和鉴别诊断流程中的应用价值。方法纳入60例临床诊断SPMD的患者设为SPMD组、9例家系成员设为家系成员组以及14例其他肌病患者设为对照组，采用亚硫酸盐测序(BSS)结合二代测序对其4qA D4Z4末端D4Z4甲基化水平进行检测和分析。结果 SPMD组患者的平均末端甲基化水平为(21.42±3.98)%。对照组平均末端甲基化水平为(64.78±5.96)%。选定其99%CI的下界值56.48%作为判定阈值，有3例高于此阈值，其余57例均有不同程度甲基化水平下降。54例经基因确诊为面肩肱型肌营养不良(FSHD)1型患者中，甲基化水平不同程度下降53例；D4Z4检测重复次数≥11次的6例患者中，4例甲基化水平降低，其中2例经全基因组测序确诊为FSHD 2型(SMCHD1基因突变)。结论 甲基化筛查有助于完善SPMD的诊断流程，对于甲基化水平降低的患者可优先进行FSHD 1型的分子检测进一步明确诊断。更多还原

【Abstract】 Aim To explore the utility of detecting 4qA D4Z4 distal methylation levels in the diagnosis and differential diagnosis process of scapuloperoneal muscular dystrophy(SPMD).Methods The study included 60 patients clinically diagnosed SPMD, 9 family members, and 14 controls with other muscular diseases. The bisulfite sequencing combined with next-generation sequencing was employed to assess and analyze the distal D4Z4 methylation levels within the 4qA D4Z4. Results The average distal methylation level in the 60 SPMD patients was(21.42±3.98)%. In the 14 non-SPMD patients, it was(64.78±5.96)%. 56.48% of the lower boundary of the 99% confidence interval was selected to determine the threshold. Among all the patients, 3 exceeded this threshold, while the remaining 57 exhibited varying degrees of decreased methylation levels. Among the 54 patients genetically confirmed as facioscapulohumeral muscular dystrophy(FSHD) type 1, 53 displayed varying degrees of decreased methylation. Among the 6 patients with D4Z4 repeat numbers ≥11, 4 showed decreased methylation levels. Additionally, two were confirmed as FSHD type 2(SMCHD1 mutation) through whole-genome sequencing. Conclusion Methylation screening contributes to refining the diagnostic process of SPMD. Patients with decreased methylation levels should be prioritized for further molecular testing to definitively diagnose FSHD type 1.更多还原