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Myasthenic syndromes due to defects in COL13A1 and in the N‐linked glycosylation pathway
Author(s) -
Beeson David,
Cossins Judith,
RodriguezCruz Pedro,
Maxwell Susan,
Liu WeiWei,
Palace Jacqueline
Publication year - 2018
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13576
Subject(s) - neuromuscular transmission , glycosylation , gene , phenotype , biology , neuromuscular junction , genetics , mutation , extracellular matrix , microbiology and biotechnology , neuroscience , endocrinology
The congenital myasthenic syndromes (CMS) are hereditary disorders of neuromuscular transmission. The number of cases recognized, at around 1:100,000 in the United Kingdom, is increasing with improved diagnosis. The advent of next‐generation sequencing has facilitated the discovery of many genes that harbor CMS‐associated mutations. An emerging group of CMS, characterized by a limb‐girdle pattern of muscle weakness, is caused by mutations in genes that encode proteins involved in the initial steps of the N‐linked glycosylation pathway, which is surprising, since this pathway is found in all mammalian cells. However, mutations in these genes may also give rise to multisystem disorders (congenital disorders of glycosylation) or muscle disorders where the myasthenic symptoms constitute only one component within a wider phenotypic spectrum. We also report a CMS due to mutations in COL13A1 , which encodes an extracellular matrix protein that is concentrated at the neuromuscular junction and highlights a role for these extracellular matrix proteins in maintaining synaptic stability that is independent of the AGRN/MuSK clustering pathway. Knowledge about the neuromuscular synapse and the different proteins involved in maintaining its structure as well as function enables us to tailor treatments to the underlying pathogenic mechanisms.