Browse by author
Lookup NU author(s): Dr Philip Nichols
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Congenital myasthenic syndrome comprises a heterogeneous group of inherited disorders of neuromuscular transmission. Acetylcholine receptor (AChR) deficiency is the most common form of congenital myasthenic syndrome and in most cases results from mutations within the coding region of the AChR « subunit. However, studies in mice have established that synapse-specific expression of AChR is dependent on a sequence contained within the AChR-subunit promoter regions, termed an N-box. We describe a consanguineous family in which 2 of 7 siblings had clinical and electromyographic features consistent with AChR deficiency. Muscle biopsy demonstrated low AChR numbers, establishing the disorder as postsynaptic. Single-strand conformational polymorphism analysis identified an abnormal conformer in the AChR «-subunit gene promoter of the patients. DNA sequence and restriction endonuclease analysis shows that the disorder cosegregates with recessive inheritance of a single point mutation, a transition (C3T) in the N-box of the «-subunit promoter. Analysis of an intercostal biopsy from 1 of the patients showed a dramatic reduction in «-subunit mRNA levels compared with disease and normal controls. This is the first evidence in humans that an N-box mutation can lead to disruption of «-subunit transcription, resulting in the loss of adult AChR synthesis and the clinical phenotype of AChR-deficiency congenital myasthenic syndrome.
Author(s): Nichols P, Croxen R, Vincent A, Rutter R, Hutchinson M, Newsom-Davis J, Beeson D
Publication type: Article
Publication status: Published
Journal: Annals of Neurology
Year: 1999
Volume: 45
Issue: 4
Pages: 439-443
ISSN (print): 0364-5134
ISSN (electronic): 1531-8249
Publisher: John Wiley & Sons, Inc.
URL: http://dx.doi.org/10.1002/1531-8249(199904)45:4<439::AID-ANA4>3.0.CO;2-W
DOI: 10.1002/1531-8249(199904)45:4<439::AID-ANA4>3.0.CO;2-W
Altmetrics provided by Altmetric
