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.