title: Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation.
abstract: BACKGROUND
  The syndrome of congenital myasthenia with episodic apnea (CMS-EA) was previously found to be due to mutations in the choline acetyltransferase gene (CHAT).
  
  
  OBJECTIVE
  To identify the mutations underlying CMS-EA in a Turkish multiplex family.
  
  
  METHODS
  Direct sequencing of the CHAT gene.
  
  
  METHODS
  A consanguineous Turkish family with 2 siblings affected by muscular weakness and episodic respiratory distress.
  
  
  RESULTS
  The sequencing of CHAT coding exons identified a previously unknown missense mutation that affected a highly conserved amino acid residue (I336T). The mutation was absent in 164 control chromosomes.
  
  
  CONCLUSIONS
  The high degree of conservation in different species strongly suggests that I336T is a functionally important amino acid residue. The absence of I336T from a large control sample further supports the pathogenic role of I336T in CMS-EA. This is the second report of CHAT mutations causing presynaptic CMS.
authors.affiliation: Institute of Human Genetics, University Hospital, Rheinische-Friedrich-Wilhelms University of Bonn, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Kraner
authors.forename: Iris
authors.initials: I
authors.lastname: Laufenberg
authors.forename: Hans M
authors.initials: HM
authors.lastname: Strassburg
authors.forename: Joern P
authors.initials: JP
authors.lastname: Sieb
authors.forename: Ortrud K
authors.initials: OK
authors.lastname: Steinlein
mesh_terms: D000328:Adult; D001049:Apnea / Q000209:etiology / Q000235:genetics*; D002648:Child; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D003241:Consanguinity; D005192:Family Health; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D020294:Myasthenic Syndromes, Congenital / Q000150:complications / Q000235:genetics*; D010375:Pedigree
chemical_list: D002795:Choline O-Acetyltransferase