title: Rapsyn N88K is a frequent cause of congenital myasthenic syndromes in European patients.
abstract: BACKGROUND
  Mutations in various genes of the neuromuscular junction may cause congenital myasthenic syndromes (CMS). Most mutations identified to date affect the epsilon-subunit gene of the acetylcholine receptor (AChR), leading to end-plate AChR deficiency. Recently, three different mutations in the RAPSN gene have been identified in four CMS patients with AChR deficiency.
  
  
  OBJECTIVE
  To perform mutation analysis of the RAPSN gene in patients with sporadic or autosomal recessive CMS.
  
  
  METHODS
  One hundred twenty CMS patients from 110 unrelated families were analyzed for the RAPSN mutation N88K by restriction fragment length polymorphism and sequence analysis.
  
  
  RESULTS
  In 12 CMS patients from 10 independent families, RAPSN N88K was identified either homozygous or heteroallelic to another missense mutation. Symptoms usually started perinatally or in the first years of life. However, one patient did not show any myasthenic symptoms before the third decade. Clinical symptoms typically included bilateral ptosis, weakness of facial, bulbar, and limb muscles, and a favorable response to anticholinesterase treatment. Crisis-like exacerbations with respiratory insufficiency provoked by stress, fever, or infections in early childhood were frequent. All RAPSN N88K families originate from Central or Western European countries. Genotype analysis indicated that they derive from a common ancestor (founder).
  
  
  CONCLUSIONS
  The RAPSN mutation N88K is a frequent cause of rapsyn-related CMS in European patients. In general, patients (RAPSN N88K) were characterized by mild to moderate myasthenic symptoms with favorable response to anticholinesterase treatment. However, severity and onset of symptoms may vary to a great extent.
authors.affiliation: Friedrich Baur Institute, Department of Neurology, and Gene Center, Ludwig Maximilians University, Munich, Germany.
authors.forename: J S
authors.initials: JS
authors.lastname: Müller
authors.forename: G
authors.initials: G
authors.lastname: Mildner
authors.forename: W
authors.initials: W
authors.lastname: Müller-Felber
authors.forename: U
authors.initials: U
authors.lastname: Schara
authors.forename: K
authors.initials: K
authors.lastname: Krampfl
authors.forename: B
authors.initials: B
authors.lastname: Petersen
authors.forename: S
authors.initials: S
authors.lastname: Petrova
authors.forename: R
authors.initials: R
authors.lastname: Stucka
authors.forename: W
authors.initials: W
authors.lastname: Mortier
authors.forename: J
authors.initials: J
authors.lastname: Bufler
authors.forename: G
authors.initials: G
authors.lastname: Kurlemann
authors.forename: A
authors.initials: A
authors.lastname: Huebner
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
authors.forename: A
authors.initials: A
authors.lastname: Abicht
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D020125:Mutation, Missense; D020294:Myasthenic Syndromes, Congenital / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment
chemical_list: D009124:Muscle Proteins; C051609:peripheral membrane protein 43K