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Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis
Author(s) -
Maselli Ricardo A.,
Chen Darlene,
Mo Delores,
Bowe Constance,
Fenton Grace,
Wollmann Robert L.
Publication year - 2003
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.10300
Subject(s) - choline acetyltransferase , acetylcholine , congenital myasthenic syndrome , myasthenia gravis , neuromuscular junction , heterozygote advantage , medicine , neuromuscular disease , mutation , endocrinology , neuromuscular transmission , genetics , disease , gene , biology , allele , neuroscience
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 demonstrated impaired neuromuscular transmission in all patients. In vitro microelectrode studies performed in the anconeus muscle biopsies of two patients showed moderate reduction of quantal release. Electron microscopy of the neuromuscular junction was normal in both patients. Each patient had two heterozygous CHAT mutations including L210P and P211A (family 1), V194L and V506L (family 2), and R548stop and S694C (family 3). Three of these mutations have previously been reported and suggest that, in this syndrome, some molecular defects may be more prevalent than others. Muscle Nerve 27: 180–187, 2003