Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome.

ABSTRACT: Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin-2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarka

SUBMITTER: Donkervoort S 

PROVIDER: S-EPMC7959540 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature