Dystrophinopathies are a group of X-linked neuromuscular disorders that result from pathogenic variants in the DMD gene. Their pathophysiological substrate is the defective expression of dystrophin in many tissues. While patients from the same pedigree usually present similar dystrophin expression and clinical course, the extent of cardiac and skeletal muscle involvement may not correlate in the same individual. We identified a new splice site variant c.2803+5G>C (NM_004006) ClinVar VCV000803902, located in intron 22 of DMD in a Brazilian family that present a broad phenotypic and histological heterogeneity. One of the subjects had a typical Duchenne muscular dystrophy (DMD) phenotype, whereas the others had Becker muscular dystrophy (BMD). Cardiac involvement was remarkable in some of the BMD patients, but not in the DMD patient. Western blot analysis of skeletal muscle revealed much lower levels of calsequestrin in the most severely affected patient compared to his brother, whose phenotype is BMD, highlighting the potential role of proteins involved in skeletal muscle calcium homeostasis in differential degrees of dystrophinopathies.

肌营养不良症是一组由DMD基因致病变异引起的 X 连锁神经肌肉疾病。它们的病理生理底物是抗肌萎缩蛋白在许多组织中的缺陷表达。虽然来自同一家系的患者通常表现出相似的肌营养不良蛋白表达和临床病程，但同一个体的心脏和骨骼肌受累程度可能不相关。我们鉴定了一个新的剪接位点变体 c.2803+5G>C (NM_004006) ClinVar VCV000803902，位于DMD的内含子 22在一个具有广泛表型和组织学异质性的巴西家庭中。其中一名受试者具有典型的 Duchenne 肌营养不良症 (DMD) 表型，而其他受试者则患有 Becker 肌营养不良症 (BMD)。一些 BMD 患者的心脏受累是显着的，但在 DMD 患者中则不然。骨骼肌的蛋白质印迹分析显示，与他的兄弟（其表型为 BMD）相比，受影响最严重的患者体内的 calsequestrin 水平要低得多，这突出了参与骨骼肌钙稳态的蛋白质在不同程度的肌营养不良症中的潜在作用。