Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis

  title={Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis},
  author={Ricardo A Maselli and Da Guang Chen and Delores Mo and Constance M. Bowe and Grace Fenton and Robert L. Wollmann},
  journal={Muscle \& Nerve},
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… 

Choline Acetyltransferase Mutations Causing Congenital Myasthenic Syndrome: Molecular Findings and Genotype–Phenotype Correlations

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.

What Have We Learned from the Congenital Myasthenic Syndromes

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.

Congenital Myasthenic Syndrome Caused by a Novel Hemizygous CHAT Mutation

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.

Clinical and Genetic Features of Congenital Myasthenic Syndromes due to CHAT Mutations: Case Report and Literature Review.

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.

A Common CHAT Gene Mutation of Congenital Myasthenic Syndrome Found in Kadazandusun Children

The diagnostic odyssey of three CMS patients from two unrelated Kadazandusun kinships and their follow-up treatment is presented, and it is postulate that p.Val306Leu may be a founder mutation in the Kadaz andusuns, an indigenous ethnic minority of Borneo Island.

A multidimensional computational exploration of congenital myasthenic syndrome causing mutations in human choline acetyltransferase

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.

Current status of the congenital myasthenic syndromes

  • A. Engel
  • Biology, Medicine
    Neuromuscular Disorders
  • 2012

Congenital myasthenic syndromes




Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans.

  • K. OhnoA. Tsujino A. Engel
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
It is reported that mutations in CHAT cause a congenital myasthenic syndrome associated with frequently fatal episodes of apnea (CMS-EA), and findings point to a defect in ACh resynthesis or vesicular filling and to CHAT as one of the candidate genes.


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Neuromuscular transmission in amyotrophic lateral sclerosis

The functional and structural characteristics of the neuromuscular junction were studied in anconeus muscle biopsies of 10 patients with amyotrophic lateral sclerosis (ALS) and decreased amplitudes of miniature endplate potentials (MEPPs) revealed.

Familial infantile myasthenia gravis: a cause of sudden death in young children.

Morphologic and immunopathologic findings in myasthenia gravis and in congenital myasthenic syndromes.

  • A. Engel
  • Medicine, Biology
    Journal of neurology, neurosurgery, and psychiatry
  • 1980
This paper focuses on ultrastructural, immunoelectron microscopic and cytochemical aspects of acquired autoimmune MG and some recently recognised congenital myasthenic syndromes.

Familial infantile myasthenia.

Familial infantile myasthenia is a potential cause of sudden infant death and should be considered in infants with unexplained respiratory distress.

Cluster of wound botulism in California: Clinical, electrophysiologic, and pathologic study

High diagnostic suspicion combined with histology and in vitro electrophysiology confirmation of presynaptic failure, especially in seronegative cases, may significantly improve morbidity.

On the release of transmitter at normal, myasthenia gravis and myasthenic syndrome affected human end‐plates.

It is concluded that the presynaptic changes, at m.p.s. end‐plates, are not the primary cause of the defect in nerve muscle transmission and are sufficient to account for failure in transmission.

In vitro microelectrode study of neuromuscular transmission in a case of botulism

In vitro microelectrode studies in the anconeus muscle biopsy of a 6‐week‐old infant intoxicated with Clostridium botulinum toxin B indicates a severe presynaptic failure of neuromuscular transmission, which appears to result from an impairment of the process of synaptic vesicle release taking place after the stimulus induced influx of calcium into the motor nerve terminals.

Familial infantile myasthenia gravis. Report of three cases with follow-up until adult life.

Recognition of FIMG has important therapeutic implications, because this disease shows rather poor response to thymectomy and steroid therapy.