scholarly journals The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndrome

2012 ◽  
Vol 21 (17) ◽  
pp. 3765-3775 ◽  
Author(s):  
Judith Cossins ◽  
Wei Wei Liu ◽  
Katsiaryna Belaya ◽  
Susan Maxwell ◽  
Michael Oldridge ◽  
...  
2004 ◽  
Vol 24 (16) ◽  
pp. 7188-7196 ◽  
Author(s):  
Marianna Rodova ◽  
Kevin F. Kelly ◽  
Michael VanSaun ◽  
Juliet M. Daniel ◽  
Michael J. Werle

ABSTRACT Rapsyn is a synapse-specific protein that is required for clustering acetylcholine receptors at the neuromuscular junction. Analysis of the rapsyn promoter revealed a consensus site for the transcription factor Kaiso within a region that is mutated in a subset of patients with congenital myasthenic syndrome. Kaiso is a POZ-zinc finger family transcription factor which recognizes the specific core consensus sequence CTGCNA (where N is any nucleotide). Previously, the only known binding partner for Kaiso was the cell adhesion cofactor, p120 catenin. Here we show that δ-catenin, a brain-specific member of the p120 catenin subfamily, forms a complex with Kaiso. Antibodies against Kaiso and δ-catenin recognize proteins in the nuclei of C2C12 myocytes and at the postsynaptic domain of the mouse neuromuscular junction. Endogenous Kaiso in C2C12 cells coprecipitates with the rapsyn promoter in vivo as shown by chromatin immunoprecipitation assay. Minimal promoter assays demonstrated that the rapsyn promoter can be activated by Kaiso and δ-catenin; this activation is apparently muscle specific. These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and δ-catenin. We propose a new model of synapse-specific transcription that involves the interaction of Kaiso, δ-catenin, and myogenic transcription factors at the neuromuscular junction.


Author(s):  
Trupti Jadhav ◽  
Poornima Shah ◽  
Purva Keni Karnavat ◽  
Anaita Udwadia Hegde

The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders arising from genetic defects in presynaptic, synaptic, and postsynaptic proteins of the neuromuscular junction (NMJ) resulting in variable and characteristically fatigable muscle weakness affecting limb, ocular, bulbar, trunk, and respiratory muscles from early life. DOK7 mutation resulting in synaptic and postsynaptic CMS clinically presents with limb-girdle myasthenia with sparing of facial and EOM. They characteristically worsen with conventional treatment and show excellent response to salbutamol/ ephedrine. Here we present a case highlighting a varied presentation beginning in late childhood and its evolution to reveal its congenital nature and subsequent management with salbutamol.


2019 ◽  
Vol 60 (6) ◽  
pp. 790-800
Author(s):  
Luana Pereira Leite Schetino ◽  
Matheus Fonseca ◽  
Matheus Proença Simão Magalhães Gomes ◽  
Priscila Aparecida Costa Valadão ◽  
Wallace Lucio Camargo ◽  
...  

2016 ◽  
Vol 30 (6) ◽  
pp. 2382-2399 ◽  
Author(s):  
Séverine M. Sigoillot ◽  
Francine Bourgeois ◽  
Jennifer Karmouch ◽  
Jordi Molgó ◽  
Alexandre Dobbertin ◽  
...  

2000 ◽  
Vol 28 (1) ◽  
pp. 82-86
Author(s):  
P. P. McConkey ◽  
A. J. Mullens

A four-month-old infant, thought to suffer from cerebral palsy, presented with respiratory failure on the background of a gradually deteriorating general level of function. Whilst being ventilated in intensive care he was noted to have severe muscle weakness. A disorder of the neuromuscular junction was suspected and he was subsequently demonstrated to have a congenital myasthenic syndrome. Anticholinesterase therapy produced a dramatic recovery. The congenital myasthenic syndromes and the diagnosis of a “floppy baby” are briefly reviewed.


2021 ◽  
pp. 1-3
Author(s):  
Setareh Alabaf ◽  
Karen O'Connell ◽  
Sithara Ramdas ◽  
David Beeson ◽  
Jacqueline Palace

Congenital Myasthenic Syndrome (CMS) are a rare group of genetic disorders of neuromuscular transmission. Some subtypes of CMS can be associated with respiratory and bulbar weakness and these patients may therefore be at high risk of developing a severe disease from COVID-19. We screened 73 patients with genetically confirmed CMS who were attending the UK national referral centre for evidence of previous Severe Acute Respiratory Syndrome Corona Virus 2 infection and their clinical outcome. Of 73 patients, seven had history of confirmed COVID-19. None of the infected patients developed a severe disease, and there were no signals that CMS alone carries a high risk of severe disease from COVID-19.


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