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Journal of Neurology

, Volume 265, Issue 3, pp 708–713 | Cite as

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 MarquesJr.
  • Roberta Paiva Magalhães Ortega
  • Marcela Câmara Machado Costa
  • André Macedo Serafim da Silva
  • Rodrigo Holanda Mendonça
  • Vitor Marques Caldas
  • Antonio Alberto Zambon
  • Osório Abath Neto
  • Paulo Eurípedes Marchiori
  • Carlos Otto Heise
  • Umbertina Conti Reed
  • Yoshiteru Azuma
  • Ana Töpf
  • Hanns Lochmüller
  • Edmar Zanoteli
Short Commentary

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.

Keywords

Congenital myasthenic syndrome Neuromuscular junction CHRNE Acetylcholine receptor Pyridostigmine 

Notes

Acknowledgements

HL received funding from the Medical Research Council (MRC) Centre for Neuromuscular Diseases UK (Reference G1002274, Grant ID 98482), by the MRC (Grant ID G0900872), the Wellcome Trust, and the European Commission through the projects NeurOmics (No. 305121) and RD-Connect (No. 305444). EPE was sponsored in part by USP (PRPG 3/2017).

Compliance with ethical standards

Ethical standards

All human studies have been approved by the local ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

Conflicts of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Eduardo de Paula Estephan
    • 1
  • Cláudia Ferreira da Rosa Sobreira
    • 2
  • André Clériston José dos Santos
    • 2
  • Pedro José Tomaselli
    • 2
  • Wilson MarquesJr.
    • 2
  • Roberta Paiva Magalhães Ortega
    • 3
  • Marcela Câmara Machado Costa
    • 4
  • André Macedo Serafim da Silva
    • 1
  • Rodrigo Holanda Mendonça
    • 1
  • Vitor Marques Caldas
    • 1
  • Antonio Alberto Zambon
    • 1
  • Osório Abath Neto
    • 1
  • Paulo Eurípedes Marchiori
    • 1
  • Carlos Otto Heise
    • 1
  • Umbertina Conti Reed
    • 1
  • Yoshiteru Azuma
    • 5
  • Ana Töpf
    • 5
  • Hanns Lochmüller
    • 5
  • Edmar Zanoteli
    • 1
  1. 1.Departamento de NeurologiaFaculdade de Medicina da Universidade de São Paulo (FMUSP)São PauloBrazil
  2. 2.Department of Neurosciences, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  3. 3.Neuropediatric DivisionFaculdade de Ciências Médicas da Santa Casa de São PauloSão PauloBrazil
  4. 4.Escola Bahiana de Medicina e Saúde PúblicaSalvadorBrazil
  5. 5.Institute of Genetic MedicineCentral ParkwayNewcastle upon TyneUK

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