Identification of previously unreported mutations in CHRNA1, CHRNE and RAPSN genes in three unrelated Italian patients with congenital myasthenic syndromes

Raffaella Brugnoni, Lorenzo Maggi, Eleonora Canioni, Isabella Moroni, Chiara Pantaleoni, Stefano D'Arrigo, Daria Riva, Ferdinando Cornelio, Pia Bernasconi, Renato Mantegazza

Research output: Contribution to journalArticle

Abstract

Congenital myasthenic syndromes are rare genetic disorders compromising neuromuscular transmission. The defects are mainly mutations in the muscle acetylcholine receptor, or associated proteins rapsyn and Dok-7. We analyzed three unrelated Italian patients with typical clinical features of congenital myasthenic syndrome, who all benefitted from cholinesterase inhibitors. We found five mutations: a previously unreported homozygous αG378D mutation in the CHRNA1 gene, a previously unreported heterozygous εY8X mutation associated with a known heterozygous εM292del deletion in the CHRNE gene, and the common heterozygous N88K mutation associated with a previously unreported heterozygous IVS1 + 2T > G splice site mutation in the RAPSN gene. All three patients had two mutant alleles; parents or offspring with a single mutated allele were asymptomatic, thus all mutations exerted their effects recessively. The previously unreported mutations are likely to reduce the number of AChRs at the motor endplate, although the αG378D mutation might produce a mild fast channel syndrome. The αG378D mutation was recessive, but recessive CHRNA1 mutations have rarely been reported previously, so studies on the effect of this mutation at the cellular level would be of interest.

Original languageEnglish
Pages (from-to)1119-1123
Number of pages5
JournalJournal of Neurology
Volume257
Issue number7
DOIs
Publication statusPublished - Jul 2010

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Congenital Myasthenic Syndromes
Mutation
Genes
Alleles
Motor Endplate
Inborn Genetic Diseases
Cholinesterase Inhibitors
Cholinergic Receptors

Keywords

  • Acetylcholine receptor
  • CHRNA1, CHRNE, and RAPSN genes
  • Congenital myasthenic syndrome
  • Rapsyn

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

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title = "Identification of previously unreported mutations in CHRNA1, CHRNE and RAPSN genes in three unrelated Italian patients with congenital myasthenic syndromes",
abstract = "Congenital myasthenic syndromes are rare genetic disorders compromising neuromuscular transmission. The defects are mainly mutations in the muscle acetylcholine receptor, or associated proteins rapsyn and Dok-7. We analyzed three unrelated Italian patients with typical clinical features of congenital myasthenic syndrome, who all benefitted from cholinesterase inhibitors. We found five mutations: a previously unreported homozygous αG378D mutation in the CHRNA1 gene, a previously unreported heterozygous εY8X mutation associated with a known heterozygous εM292del deletion in the CHRNE gene, and the common heterozygous N88K mutation associated with a previously unreported heterozygous IVS1 + 2T > G splice site mutation in the RAPSN gene. All three patients had two mutant alleles; parents or offspring with a single mutated allele were asymptomatic, thus all mutations exerted their effects recessively. The previously unreported mutations are likely to reduce the number of AChRs at the motor endplate, although the αG378D mutation might produce a mild fast channel syndrome. The αG378D mutation was recessive, but recessive CHRNA1 mutations have rarely been reported previously, so studies on the effect of this mutation at the cellular level would be of interest.",
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AU - Brugnoni, Raffaella

AU - Maggi, Lorenzo

AU - Canioni, Eleonora

AU - Moroni, Isabella

AU - Pantaleoni, Chiara

AU - D'Arrigo, Stefano

AU - Riva, Daria

AU - Cornelio, Ferdinando

AU - Bernasconi, Pia

AU - Mantegazza, Renato

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