隐性肌病很少见,通常表现为严重的早发性肌病。在这里,我们报告了来自印度南部的三名无关患者的轻度表型(2M,1F)16岁、21岁和22岁,他出现了童年发作,逐步推进,疲劳肢体腰带无力,上睑下垂,说话和吞咽困难,没有心脏参与.血清肌酸激酶升高,重复神经刺激显示全部减少。在两名患者中,吡啶斯的明和沙丁胺醇的临床改善。所有三名患者在内含子5中具有纯合替换:DES(NM_001927.4):c.10235G>A,预测会导致供体剪接部位缺损。肌肉活检与超微结构分析提示肌病伴肌原纤维紊乱,免疫组织化学显示结蛋白部分丢失,有一些残留染色,而蛋白质印迹分析显示结蛋白减少。患者肌肉RNA的RT-PCR揭示了两种转录本:正常结蛋白转录本减少,异常转录本增加,表明内含子5供体位点有渗漏剪接。PCR产物的测序证实了在较长的转录物中包含内含子5,预测会导致过早的终止密码子。因此,我们提供的证据表明,剪接部位的渗漏导致结蛋白部分丢失,这与轻度结蛋白相关隐性肌病的独特表型表现相关,并与先天性肌无力综合征重叠.
Recessive desminopathies are rare and often present as severe early-onset myopathy. Here we report a milder phenotype in three unrelated patients from southern India (2 M, 1F) aged 16, 21, and 22 years, who presented with childhood-onset, gradually progressive, fatigable limb-girdle weakness, ptosis, speech and swallowing difficulties, without cardiac involvement. Serum creatine kinase was elevated, and repetitive nerve stimulation showed decrement in all. Clinical improvement was noted with pyridostigmine and salbutamol in two patients. All three patients had a homozygous substitution in intron 5: DES(NM_001927.4):c.1023+5G>A, predicted to cause a donor splice site defect. Muscle biopsy with ultrastructural analysis suggested myopathy with myofibrillar disarray, and immunohistochemistry showed partial loss of desmin with some residual staining, while western blot analysis showed reduced desmin. RT-PCR of patient muscle RNA revealed two transcripts: a reduced normal desmin transcript and a larger abnormal transcript suggesting leaky splicing at the intron 5 donor site. Sequencing of the PCR products confirmed the inclusion of intron 5 in the longer transcript, predicted to cause a premature stop codon. Thus, we provide evidence for a leaky splice site causing partial loss of desmin associated with a unique phenotypic presentation of a milder form of desmin-related recessive myopathy overlapping with congenital myasthenic syndrome.