title: AChR deficiency due to epsilon-subunit mutations: two common mutations in the Netherlands.
abstract: 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) epsilon-subunit gene underlying congenital myasthenic syndromes in nine patients (seven kinships) of Dutch origin. Previously reported mutations epsilon1369delG and epsilonR311Q were found to be common; epsilon1369delG was present on at least one allele in seven of the nine patients, and epsilonR311Q in six. Phenotypes ranged from relatively mild ptosis and external ophthalmoplegia to generalized myasthenia. The common occurrence of epsilonR311Q and epsilon1369delG 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 epsilonR311Q and epsilon1369delG.
authors: Department of Neurology, Maastricht University Medical Centre, PO Box 5800, 6202 AZ, Maastricht, The Netherlands. c.faber@mumc.nl
authors: Catharina G
authors: CG
authors: Faber
authors: Peter C
authors: PC
authors: Molenaar
authors: Johannes S H
authors: JS
authors: Vles
authors: Domenic M
authors: DM
authors: Bonifati
authors: Jan J G M
authors: JJ
authors: Verschuuren
authors: Pieter A
authors: PA
authors: van Doorn
authors: Jan B M
authors: JB
authors: Kuks
authors: John H J
authors: JH
authors: Wokke
authors: David
authors: D
authors: Beeson
authors: Marc
authors: M
authors: De Baets
mesh_terms: D017668:Age of Onset; D000483:Alleles; D001763:Blepharoptosis / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics*; D009426:Netherlands; D009886:Ophthalmoplegia / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000172:deficiency* / Q000235:genetics*
chemical_list: C504423:CHRNE protein, human; D011978:Receptors, Nicotinic