DMD基因内含子突变致Becker型肌营养不良1例报告并文献复习

Becker Muscular Dystrophy Caused by an Intron Mutation in the DMD Gene: A Case Report and Literature Review

摘要: 目的：探讨DMD基因内含子突变所致Becker型肌营养不良(BMD)的临床表现及基因变异特征。方法：回顾分析1例确诊BMD患儿的临床资料、肌肉病理及基因检测结果并复习相关文献。结果：患儿，男，12岁，2年前活动后出现乏力伴双下肢不适感，小便如茶色，急性期肌酸激酶、肌红蛋白水平可升高至正常值100倍以上；尿液分析示隐血3+，红细胞计数正常；代谢缺陷筛查(血、尿有机酸分析)无异常。后患儿乏力及尿液异常反复发生，全外显子检测无DMD基因相关突变；肌肉病理示骨骼肌呈肌病样改变，Dystrophin表达下降；DMD基因mRNA测序示存在异常剪接。患儿最终确诊为BMD。结论：反复横纹肌溶解的患者亦应考虑BMD的可能；对DMD基因外显子检测无异常，但Dystrophin表达异常的患者，需警惕内含子突变所致基因异常剪接。

Abstract: Objective: To investigate the clinical manifestation and gene variation of Becker muscular dystro-phy (BMD) caused by intron mutation of DMD gene. Methods: The clinical data, muscle pathology and gene detection results of one child with confirmed BMD were analyzed retrospectively and the related literature was reviewed. Results: A 12-year-old male patient developed fatigue with dis-comfort in both lower limbs after activity 2 years ago, with a brown urine color. In the acute phase, the levels of creatine kinase and myoglobin can increase to over 100 times the normal value; Urine analysis showed occult blood 3+ and normal red blood cell count; Metabolic defect screening (blood and urine organic acid analysis) showed no abnormalities. The patient experienced recurrent fa-tigue and urinary abnormalities, and no DMD gene related mutations were detected in the whole exon; Muscle pathology showed myopathic changes in skeletal muscles, with a decreased expres-sion of dystrophin. The mRNA sequencing of the DMD gene showed abnormal splicing. The patient was ultimately diagnosed with BMD. Conclusion: Patients with recurrent rhabdomyolysis should also consider the possibility of BMD; patients with DMD gene exon detection without abnormalities, but dystrophin expression abnormalities, should be vigilant for gene splicing caused by intron mu-tations.