MYASTHENIC SYNDROMES IN TURKISH KINSHIPS DUE TO MUTATIONS IN THE ACETYLCHOLINE-RECEPTOR

We report and functionally characterize live new mutations of the acet ylcholine receptor (AChR) in 11 Turkish patients with recessive congen ital myasthenic syndromes (CMS) belonging to six families. All mutatio ns are in the epsilon-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 th e epsilon subunit, and one occurs at a splice donor site. Expression o f each frameshifting mutation and the likely transcripts of the splice -site mutation in human embryonic kidney 293 cells shows that each mut ation is a null mutation. The findings support the notion that loss-of -function mutations of the acetylcholine receptor causing CMS are conc entrated in the epsilon subunit, and that such mutations are a frequen t cause of CMS.