We report and functionally characterize five new mutations of the acetylcholine receptor (AChR) in 11 Turkish patients with recessive congenital myasthenic syndromes (CMS) belonging to six families. All mutations are in the ε-subunit gene. Parental consanguinity is present in three families. The disease cosegregates with homozygous mutations in five families and with two different heteroallelic mutations in one family. Four mutations are frameshifting, predicting truncation of the ε subunit, and one occurs at a splice donor site. Expression of each frameshifting mutation and the likely transcripts of the splice-site mutation in human embryonic kidney 293 cells shows that each mutation is a null mutation. The findings support the notion that loss-of-function mutations of the acetylcholine receptor causing CMS are concentrated in the ε subunit, and that such mutations are a frequent cause of CMS.
ASJC Scopus subject areas
- Clinical Neurology