Abstract：
Early onset myopathies are a clinically and histologically heterogeneous monogenic diseases linked to approximately 90 genes. Molecular diagnosis is challenging, especially in patients with a mild phenotype. We describe a 26-year-old man with neonatal hypotonia, motor delay and seizures during infancy, and non-progressive, mild muscular weakness in adulthood. Serum Creatine kinase level was normal. Whole-body muscle MRI showed thin muscles, and brain MRI was unremarkable. A deltoid muscle biopsy showed glycogen storage. WGS revealed a de novo 1.4 Mb-deletion of chromosome 14, confirmed by Array-CGH. This microdeletion causes the loss of ten genes including RALGAPA1, encoding for RalA, a regulator of glucose transporter 4 (GLUT4) expression at the membrane of myofibers. GLUT4 was overexpressed in patient\'s muscle. Here we highlight the importance to search for chromosomal alterations in the diagnostic workup of early onset myopathies.
摘要：
早发性肌病是与大约90个基因相关的临床和组织学异质性单基因疾病。分子诊断具有挑战性,尤其是轻度表型的患者。我们描述了一个26岁的新生儿张力减退患者,婴儿期运动延迟和癫痫发作，和非进步，成年期轻度肌肉无力。血清肌酸激酶水平正常。全身肌肉MRI显示肌肉薄，脑MRI并不显著。三角肌活检显示糖原储存。WGS显示14号染色体从头1.4Mb缺失，经Array-CGH证实。这种微缺失导致10个基因的丢失，包括RALGAPA1，编码RalA，肌纤维膜上葡萄糖转运蛋白4（GLUT4）表达的调节因子。GLUT4在患者肌肉中过度表达。在这里，我们强调了在早发性肌病的诊断检查中寻找染色体改变的重要性。
