Molecular characterisation of congenital myasthenic syndromes in Southern Brazil

Objective To perform genetic testing of patients with congenital
myasthenic syndromes (CMS) from the Southern Brazilian state of
Parana. Patients and methods Twenty-five CMS patients from 18
independent families were included in the study. Known CMS genes
were sequenced and restriction digest for the mutation RAPSN p.N88K
was performed in all patients. Results We identified recessive
mutations of CHRNE in ten families, mutations in DOK7 in three
families and mutations in COLQ, CHRNA1 and CHRNB1 in one family
each. The mutation CHRNE c. 70insG was found in six families. We
have repeatedly identified this mutation in patients from Spain and
Portugal and haplotype studies indicate that CHRNE c. 70insG
derives from a common ancestor. Conclusions Recessive mutations in
CHRNE are the major cause of CMS in Southern Brazil with a common
mutation introduced by Hispanic settlers. The second most common
cause is mutations in DOK7. The minimum prevalence of CMS in Parana
is 0.18/100 000.