AChR deficiency due to ε-subunit mutations: two common mutations in the Netherlands

Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) ε-subunit gene underlying congenital myasthenic syndromes in nine patients (seven k...

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Bibliographic Details
Published in:Journal of neurology 2009-10, Vol.256 (10), p.1719-1723
Main Authors: Faber, Catharina G., Molenaar, Peter C., Vles, Johannes S. H., Bonifati, Domenic M., Verschuuren, Jan J. G. M., van Doorn, Pieter A., Kuks, Jan B. M., Wokke, John H. J., Beeson, David, De Baets, Marc
Format: Article
Language:English
Subjects:
Age of Onset
Alleles
Biological and medical sciences
Blepharoptosis - genetics
Child, Preschool
Diseases of striated muscles. Neuromuscular diseases
DNA Mutational Analysis
Family
Female
Humans
Infant
Infant, Newborn
Male
Medical sciences
Medicine
Medicine & Public Health
Mutation
Myasthenic Syndromes, Congenital - genetics
Netherlands
Neurology
Neuroradiology
Neurosciences
Ophthalmoplegia - genetics
Original Communication
Pedigree
Phenotype
Polymorphism, Single Nucleotide
Receptors, Nicotinic - deficiency
Receptors, Nicotinic - genetics
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Summary:Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) ε-subunit gene underlying congenital myasthenic syndromes in nine patients (seven kinships) of Dutch origin. Previously reported mutations ε1369delG and εR311Q were found to be common; ε1369delG was present on at least one allele in seven of the nine patients, and εR311Q in six. Phenotypes ranged from relatively mild ptosis and external ophthalmoplegia to generalized myasthenia. The common occurrence of εR311Q and ε1369delG suggests a possible founder for each of these mutations originating in North Western Europe, possibly in Holland. Knowledge of the ethnic or geographic origin within Europe of AChR deficiency patients can help in targeting genetic screening and it may be possible to provide a rapid genetic diagnosis for patients of Dutch origin by screening first for εR311Q and ε1369delG.
ISSN:0340-5354
1432-1459
DOI:10.1007/s00415-009-5190-7