title: Congenital myasthenic syndromes: clinical and genetic analysis of 18 patients.
abstract: Congenital myasthenic syndromes (CMS) are a group of rare gentic disorders in which neuromuscular transmission is compromised by a variety of mechanisms, other than autoimmunity. Recently, substantial progress has been made by the identification of mutations in acetylcholine receptor (AChR) genes which cause CMS. We report on the clinical and genetic analysis of 18 independent CMS patients. All patients were clinically classified as sporadic cases of CMS (group III according to ENMC consensus). In order to investigate the prevalence of AChR mutations in this group we analyzed structural domains of the AChR genes at strategically important sites - the channel pore-lining regions (M2 domains) of the alpha, beta and epsilon subunits, and the extracellular domain close the acetylcholine (ACh) binding site. All patients showed wild-type sequence in these regions, mutations were not detected. Therefore, we conclude, that point mutations in domains which are known to cause slow channel congenital myasthenic syndromes (SCCMS) are rare in group III-patients in Germany. Determining the genetic defects causing CMS may have implications for diagnosis and genetic counseling of CMS patients. Moreover, this may be important for the therapeutic management of CMS as some patients may profit form quinidine sulfate. Therefore, further efforts will be undertaken to elucidate the underlying defects of CMS.
authors.affiliation: Friedrich-Baur-Institut, Ludwig-Maximilians-Universitat Munchen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Abicht
authors.forename: W
authors.initials: W
authors.lastname: Müller-Felber
authors.forename: P
authors.initials: P
authors.lastname: Fischer
authors.forename: I
authors.initials: I
authors.lastname: Jakob
authors.forename: L
authors.initials: L
authors.lastname: Kürz
authors.forename: R
authors.initials: R
authors.lastname: Rudel
authors.forename: W
authors.initials: W
authors.lastname: Mortier
authors.forename: D
authors.initials: D
authors.lastname: Pongratz
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D009157:Myasthenia Gravis / Q000151:congenital / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013577:Syndrome
chemical_list: D002800:Cholinesterase Inhibitors