Congenital myasthenic syndrome due to a <i>TOR1AIP1</i> mutation: a new disease pathway for impaired synaptic transmission.

ABSTRACT: Congenital myasthenic syndromes are inherited disorders characterized by fatiguable muscle weakness resulting from impaired signal transmission at the neuromuscular junction. Causative mutations have been identified in genes that can affect the synaptic function or structure. We identified a homozygous frameshift deletion c.127delC, p. Pro43fs in TOR1AIP1 in two siblings with limb-girdle weakness and impaired transmission at the neuromuscular synapse. TOR1AIP1 encodes the inner nuclear membrane protein lamin-associated protein 1. On muscle biopsy from the index case, lamin-associated protein 1 was absent from myonuclei. A mouse model with lamin-associated protein 1 conditionally knocked out in striated muscle was used to analyse the role of lamin-associated protein 1 in synap

SUBMITTER: Cossins J 

PROVIDER: S-EPMC7660151 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature