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.

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.

• Authors: Simone Kraner, Iris Laufenberg, Hans M Strassburg, Joern P Sieb, Ortrud K Steinlein
• Journal: Archives of neurology (Arch Neurol) Vol. 60 Issue 5 Pg. 761-3 (May 2003) ISSN: 0003-9942 [Print] United States
• PMID: 12756141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Choline O-Acetyltransferase

Topics

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