A common CHRNE mutation (c.130dupG) in Brazilian patients with congenital myasthenic syndrome

CHRNE mutations account for approximately 50% of all congenital myasthenic syndrome (CMS). Although there are several CHRNE mutations described, some pathogenic allelic variants are especially frequent in certain ethnic groups. In Brazil a study held at the South of the country showed the CHRNE mutation c.130dupG as a quite prevalent cause of CMS, with a possible founder effect. To verify the frequency of this mutation among patients from other regions of the country and characterize clinical features of these patients. Fifty four CMS patients from 44 families were clinically evaluated and had DNA samples underwent to sequencing of the exon 2 of CHRNE. The mutation c.130dupG was found in 22 patients (16 families), being 17 patients (13 families) in homozygous fashion. All patients presented with early onset of symptoms, good response to pyridostigmine, fluctuating symptoms, ocular motor impairment (OMI) and ptosis (PP). Maintenance of good functionality (95%), appendicular weakness (AW) (86%), bulbar symptoms (77%) and ial involvement (73%) were also very frequent. Electromyography was recorded in 16 patients: 12 showed decremental reponse. Of the remaining 4 cases, 2 underwent single fiber study, which showed increased of Jitter in both. The frequency of mutation among CMS patients was 40.7%, accounting for 36% of the families. Selecting only patients with OMI, PP and AW, the chance of finding the mutation was 63%. The clinical features presented are expected in patients with CHRNE mutation. However, some of them were especially frequent in the cases with the studied mutation. The CHRNE mutation c.130dupG is very common in patients with CMS from different regions of Brazil, and should be the first investigated within the molecular diagnostic strategy for CMS patients from this origin.