Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation

Arch Neurol. 2003 May;60(5):761-3. doi: 10.1001/archneur.60.5.761.


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.

Design: Direct sequencing of the CHAT gene.

Patients: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apnea / etiology
  • Apnea / genetics*
  • Child
  • Choline O-Acetyltransferase / genetics*
  • Consanguinity
  • Family Health
  • Female
  • Homozygote
  • Humans
  • Male
  • Mutation, Missense*
  • Myasthenic Syndromes, Congenital / complications
  • Myasthenic Syndromes, Congenital / genetics*
  • Pedigree


  • Choline O-Acetyltransferase