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Neurology 1999;53:1564
© 1999 American Academy of Neurology
Articles

A common mutation ({epsilon}1267delG) in congenital myasthenic patients of Gypsy ethnic origin

A. Abicht, MD, R. Stucka, PhD, V. Karcagi, PhD, A. Herczegfalvi, MD, R. Horváth, MD, W. Mortier, MD, U. Schara, MD, V. Ramaekers, MD, W. Jost, MD, J. Brunner, MD, G. Janßen, MD, U. Seidel, MD, B. Schlotter, MD, W. Müller-Felber, MD, D. Pongratz, MD, R. Rüdel, PhD and H. Lochmüller, MD

From the Genzentrum und Friedrich-Baur-Institut (Drs. Abicht, Stucka, Horváth, Schlotter, Müller-Felber, Pongratz, and Lochmüller), LMU München, Germany; the Department of Biochemistry (Dr. Karcagi), National Institute of Environmental Health, Budapest; Heim Pal Pediatric Hospital (Dr. Herczegfalvi), Budapest, Hungary; Universitätskinderklinik und Neuromuskuläres Labor (Drs. Mortier and Schara), Ruhr-Universität Bochum, Germany; the Neuropädiatrie (Dr. Ramaekers), Rheinisch-Westfälische Technische Hochschule Aachen, Germany; the Universitätsklinik für Kinder und Jugendmedizin (Drs. Jost and Brunner), Homburg/Saar, Germany; the Neuropädiatrie (Dr. Janßen), Universitätskinderklinik, Heinrich-Heine Universität, Düsseldorf, Germany; the Klinik für Pädiatrie mit Schwerpunkt Neurologie (Dr. Seidel), Universitätsklinikum Charité, Berlin, Germany; and the Abt. für Allgemeine Physiologie (Dr. Rüdel), Universität Ulm, Germany.

Address correspondence and reprint requests to Dr. Hanns Lochmüller, Genzentrum München, Feodor-Lynen-Str. 25, 81377 München, Germany.

OBJECTIVE: Mutation analysis of the acetylcholine receptor (AChR) {epsilon} subunit gene in patients with sporadic or autosomal recessive congenital myasthenic syndromes (CMS).

BACKGROUND: The nicotinic AChR of skeletal muscle is a neurotransmitter-gated ion channel that mediates synaptic transmission at the vertebrate neuromuscular junction. Mutations in its gene may cause congenital myasthenic syndromes. A recently described mutation in exon 12 of the AChR {epsilon} subunit ({epsilon}1267delG) disrupts the cytoplasmic loop and the fourth transmembrane region (M4) of the AChR {epsilon} subunit.

METHODS: Forty-three CMS patients from 35 nonrelated families were clinically classified as sporadic cases of CMS (group III according to European Neuromuscular Centre consensus) and were analyzed for {epsilon}1267delG by PCR amplification and sequence analysis.

RESULTS: The authors report the complete genomic sequence and organization of the gene coding for the {epsilon} subunit of the human AChR (accession number AF105999). Homozygous {epsilon}1267delG was identified in 13 CMS patients from 11 independent families. All {epsilon}1267delG families were of Gypsy or southeastern European origin. Genotype analysis indicated that they derive from a common ancestor (founder) causing CMS in the southeastern European Gypsy population. Phenotype analysis revealed a uniform pattern of clinical features including bilateral ptosis and mild to moderate fatigable weakness of ocular, facial, bulbar, and limb muscles.

CONCLUSIONS: The mutation {epsilon}1267delG might be frequent in European congenital myasthenic syndrome patients of Gypsy ethnic origin. In general, patients ({epsilon}1267delG) were characterized by the onset of symptoms in early infancy, the presence of ophthalmoparesis, positive response to anticholinesterase treatment, and the benign natural course of the disease.

Key words: Congenital myasthenic syndrome—Acetylcholine receptor {epsilon} subunit—Neuromuscular junction—Neuropediatrics.




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