Objectives: To describe the clinical and genetic features of a Chinese congenital myasthenic syndromes (CMS) patient with two novel missense mutations in muscle specific receptor tyrosine kinase (MUSK) gene and review 15 MUSK-related CMS patients from 8 countries.
Methods: The patient was a 30-year-old man with chronic progressively proximal limb weakness for 22 years and diagnosed as muscular dystrophy before. Serum creatine kinase (CK) was normal. Repetitive nerve stimulation (RNS) test showed decrements at low rate stimulation. Weakness became worse after conventional doses of pyridostigmine. Mild multiple atrophy of thigh and leg muscle was observed in MRI. Open muscle biopsy and genetic analysis were performed. One hundred healthy individuals were set for control.
Results: Muscle biopsy showed mild variation in fiber size. Two missense mutations in MUSK gene (p.P650T and p.I795S) were identified in the patient. The mutation of p.I795S was identified in his father and p.P650T in his mother. Both of them were not detected among the healthy controls and predicted to be damaging or disease causing by prediction tools.
Conclusion: In this study, we identified a limb-girdle CMS (LG-CMS) patient carrying two novel heterozygous missense mutations in MUSK gene. CMS related genes should be analyzed in patients with limb-girdle weakness, normal CK, decrement of CMAP at RNS and mild change in muscle biopsy or MRI.
Keywords: Congenital myasthenic syndrome; Limb-girdle CMS; MUSK gene; Missense mutations; Neuromuscular transmission.
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