Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of rare diseases caused by dysfonction of neuromuscular transmission and share common clinical features characterized by fluctuation of muscle weakness and fatigability. Identification of mutations in genes encoding neuromuscular junction (NMJ) proteins has intensified in recent years. However in French cohort, some of CMS patients are still genetically undiagnosed. These last years, using whole exome sequencing and sanger sequencing, we identify for the first time mutations in SLC5A7 encoding the presynaptic sodium dependant hight-affinity choline transporter 1 (CHT1) responsible of severe CMS with episodic apnea (CMS-EA) and one the other hand new mutations in GFPT1 encoding an enzyme involved in glycosylated of ubiquitous proteins causing limb-girdle CMS with tubular aggregates. In the first study, we identified 11 recessive mutations in SLC5A7 that are associated with a spectrum of severe muscle weakness ranging from a lethal antenatal form of arthrogryposis and severe hypotonia to a neonatal form of CMS-EA. The missense mutations induced a near complete loss of function of CHT activity in cell models. At the human NMJ, a delay in synaptic maturation and an altered maintenance were observed in the antenatal and neonatal forms, respectively. In the second study, we identified 9 new GFPT1 mutations and we report the first retrospective clinical evaluation of LG-CMS individuals stresses an evolution toward a myopathic weakness that occurs concomitantly to ineffectiveness of usual CMS treatments. Analysis of neuromuscular biopsies from 3 unrelated individuals demonstrates that the maintenance of NMJs is dramatically impaired with loss of post-synaptic junctional folds and evidence of denervation-reinnervation processes affecting the 3 main NMJ components. Moreover, molecular analyses of the human muscle biopsies confirm glycosylation defects of proteins with reduced O-glycosylation and show reduced sialylation of transmembrane proteins in extrajunctional area. His two studies highlighted that CHT1 is the second most frequent gene after CHAT responsible of CMS-EA and reinforced that GFPT1 is the primary genetic cause of ubiquitous CMS. This work has allowed to widen the genetic and clinical spectrum of CMS whose phenotypic complexity that could be only a small part of a much more extensive disease phenotype.