Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis

@article{Maselli2003CholineAM,
  title={Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis},
  author={R. Maselli and Darlene Chen and Delores Mo and C. Bowe and G. Fenton and R. Wollmann},
  journal={Muscle \& Nerve},
  year={2003},
  volume={27}
}
The myasthenic syndrome due to abnormal acetylcholine resynthesis is characterized by early onset, recessive inheritance, and recurrent episodes of potentially fatal apnea. Mutations in the gene encoding choline acetyltransferase (CHAT) have been found to account for this condition. We have identified five patients from three independent families with features of this disease including, in four patients, a paradoxical worsening of symptoms with cold temperatures. Electrodiagnostic studies… Expand
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Choline Acetyltransferase Mutations Causing Congenital Myasthenic Syndrome: Molecular Findings and Genotype–Phenotype Correlations
TLDR
The characterization of mutants showed a decrease in the overall catalytic efficiency of ChAT; in particular, those located near the active‐site tunnel produced the most seriously disruptive phenotypic effects. Expand
What Have We Learned from the Congenital Myasthenic Syndromes
TLDR
After a series of patients carrying mutations in a disease gene have been identified, the emerging genotype–phenotype correlations provided clues for targeted mutation analysis in other patients. Expand
Clinical variability of CMS-EA (congenital myasthenic syndrome with episodic apnea) due to identical CHAT mutations in two infants.
  • N. Barišić, J. Müller, +7 authors A. Abicht
  • Medicine
  • European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
  • 2005
TLDR
Se sequencing of the CHAT gene revealed identical, compound heterozygous mutations S694C and T354M in both children, in line with a remarkable clinical heterogeneity observed in patients with CHAT mutations and emphasize the potential role of apneic crises for the development of secondary hypoxic brain damage and psychomotor retardation. Expand
Congenital Myasthenic Syndrome Caused by a Novel Hemizygous CHAT Mutation
TLDR
The alignment of amino acid sequences revealed that glutamine at codon 659 is highly conserved in different species and causes structural changes in the substrate-binding site, which may help to further elucidate clinical features and treatment methods in neonate-onset CMS caused by CHAT gene mutations. Expand
Clinical and Genetic Features of Congenital Myasthenic Syndromes due to CHAT Mutations: Case Report and Literature Review.
TLDR
The genetic and clinical findings in 44 CMS patients due to CHAT mutations in the literature up to date are described and appropriate treatment can improve morbidity and mortality. Expand
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment
TLDR
Greater understanding of the mechanisms of CMS have been obtained from structural and electrophysiological studies of the endplate, and from biochemical studies, and present therapies for the CMS include cholinergic agonists, long-lived open-channel blockers of the acetylcholine receptor ion channel, and adrenergic agonist. Expand
Chapter 99 – Congenital Myasthenic Syndromes
TLDR
Congenital myasthenic syndromes can also occur in combination with centronuclear myopathy defects in plectin, and the molecular basis of some phenotypically characterized CMS remains elusive. Expand
A multidimensional computational exploration of congenital myasthenic syndrome causing mutations in human choline acetyltransferase
TLDR
This study systematically sift through the available genetic data in search of previously unreported pathogenic mutations and uses a dynamic in silico model to provide structural explanations for the pathogenicity of the reported deleterious and undetermined variants. Expand
Current status of the congenital myasthenic syndromes
  • A. Engel
  • Medicine, Biology
  • Neuromuscular Disorders
  • 2012
TLDR
Congenital myasthenic syndromes associated with centronuclear myopathies were recently recognized and analysis of properties of expressed mutant proteins contributed to finding improved therapy for most CMS. Expand
Congenital myasthenic syndromes
TLDR
In this article, a strategy that leads to the diagnosis of congenital myasthenic syndromes is presented, and recent advances in the clinical, genetic and molecular aspects of Congenital myASThenic syndrome are outlined. Expand
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