title: Molecular characterisation of congenital myasthenic syndromes in Southern Brazil.
abstract: OBJECTIVE
  To perform genetic testing of patients with congenital myasthenic syndromes (CMS) from the Southern Brazilian state of Parana.
  
  
  METHODS
  Twenty-five CMS patients from 18 independent families were included in the study. Known CMS genes were sequenced and restriction digest for the mutation RAPSN p.N88K was performed in all patients.
  
  
  RESULTS
  We identified recessive mutations of CHRNE in ten families, mutations in DOK7 in three families and mutations in COLQ, CHRNA1 and CHRNB1 in one family each. The mutation CHRNE c.70insG was found in six families. We have repeatedly identified this mutation in patients from Spain and Portugal and haplotype studies indicate that CHRNE c.70insG derives from a common ancestor.
  
  
  CONCLUSIONS
  Recessive mutations in CHRNE are the major cause of CMS in Southern Brazil with a common mutation introduced by Hispanic settlers. The second most common cause is mutations in DOK7. The minimum prevalence of CMS in Parana is 0.18/100 000.
authors.affiliation: Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Newcastle upon Tyne, UK. hanns.lochmuller@newcastle.ac.uk
authors.forename: V
authors.initials: V
authors.lastname: Mihaylova
authors.forename: R H
authors.initials: RH
authors.lastname: Scola
authors.forename: B
authors.initials: B
authors.lastname: Gervini
authors.forename: P J
authors.initials: PJ
authors.lastname: Lorenzoni
authors.forename: C K
authors.initials: CK
authors.lastname: Kay
authors.forename: L C
authors.initials: LC
authors.lastname: Werneck
authors.forename: R
authors.initials: R
authors.lastname: Stucka
authors.forename: V
authors.initials: V
authors.lastname: Guergueltcheva
authors.forename: M
authors.initials: M
authors.lastname: von der Hagen
authors.forename: A
authors.initials: A
authors.lastname: Huebner
authors.forename: A
authors.initials: A
authors.lastname: Abicht
authors.forename: J S
authors.initials: JS
authors.lastname: Müller
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics*; D010375:Pedigree