title: A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin.
abstract: 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 (epsilon1267delG) 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 epsilon1267delG 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 epsilon1267delG was identified in 13 CMS patients from 11 independent families. All epsilon1267delG 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 epsilon1267delG might be frequent in European congenital myasthenic syndrome patients of Gypsy ethnic origin. In general, patients (epsilon1267delG) 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.
authors.affiliation: Genzentrum und Friedrich-Baur Institut, LMU München, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Abicht
authors.forename: R
authors.initials: R
authors.lastname: Stucka
authors.forename: V
authors.initials: V
authors.lastname: Karcagi
authors.forename: A
authors.initials: A
authors.lastname: Herczegfalvi
authors.forename: R
authors.initials: R
authors.lastname: Horváth
authors.forename: W
authors.initials: W
authors.lastname: Mortier
authors.forename: U
authors.initials: U
authors.lastname: Schara
authors.forename: V
authors.initials: V
authors.lastname: Ramaekers
authors.forename: W
authors.initials: W
authors.lastname: Jost
authors.forename: J
authors.initials: J
authors.lastname: Brunner
authors.forename: G
authors.initials: G
authors.lastname: Janssen
authors.forename: U
authors.initials: U
authors.lastname: Seidel
authors.forename: B
authors.initials: B
authors.lastname: Schlotter
authors.forename: W
authors.initials: W
authors.lastname: Müller-Felber
authors.forename: D
authors.initials: D
authors.lastname: Pongratz
authors.forename: R
authors.initials: R
authors.lastname: Rüdel
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005060:Europe / Q000208:ethnology; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020294:Myasthenic Syndromes, Congenital / Q000208:ethnology* / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D011950:Receptors, Cholinergic / Q000235:genetics; D006178:Romani People / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D011950:Receptors, Cholinergic