Congenital myasthenic syndrome due to compound heterozygous mutations in the GFPT1 gene

Abstract Congenital myasthenic syndrome (CMS) is a heterogeneous group of hereditary neuromuscular disorders associated with neuromuscular junction (NMJ) dysfunction. Here, we report the genetic variants and clinical follow-up of one individual suffering from CMS. The proband presented with limb weakness, and symptoms worsened after limb activities. In addition, decreases in muscle action potential were observed with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but the patient did not experience drooping eyelids or blurred vision. Trio whole exome sequencing was performed for the proband and his parents. We found two different heterozygous missense variants (c.331C>T; p.Arg111Cys and c.1428G>C; p.Lys476Asn) in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in this patient with autosomal recessive CMS, of which one was novel. The new c.1428G>C; p.Lys476Asn variant has not been previously reported, and has not been recorded in the ClinVar dataset or the gnomAD global population dataset. The phenotypes （proximal muscle weakness and fatigue while ocular and facial involvement is only minimal，limb-girdle weakness and fatigue.，beneficial and sustained response to acetylcholinesterase inhibitor treatment）of the proband were consistent with those previously reported for CMS. Our study provides important information for the diagnosis and treatment of patients with CMS.