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A common CHRNE mutation in Brazilian patients with congenital myasthenic syndrome
Journal article   Peer reviewed

A common CHRNE mutation in Brazilian patients with congenital myasthenic syndrome

Eduardo de Paula Estephan, Cláudia Ferreira da Rosa Sobreira, André Clériston José Dos Santos, Pedro José Tomaselli, Wilson Marques Jr, Roberta Paiva Magalhães Ortega, Marcela Câmara Machado Costa, André Macedo Serafim da Silva, Rodrigo Holanda Mendonça, Vitor Marques Caldas, …
Journal of neurology, Vol.265(3), pp.708-713
03/2018
DOI: 10.1007/s00415-018-8736-8
PMCID: PMC7115868
PMID: 29383513
url
http://dx.doi.org/10.1007/s00415-018-8736-8View
Open Access

Abstract

The most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity.
 Family Mutation Phenotype Adolescent Adult Age of Onset Aged Brazil - epidemiology Child Child, Preschool Cohort Studies Exons Female Humans Male Middle Aged Myasthenic Syndromes, Congenital - drug therapy Myasthenic Syndromes, Congenital - epidemiology Myasthenic Syndromes, Congenital - genetics Myasthenic Syndromes, Congenital - pathology Prevalence Receptors, Nicotinic - genetics Young Adult

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