Congenital myasthenic syndrome caused by a mutation in the Ets-binding site of the promoter region of the acetylcholine receptor ε subunit gene

K. Ohno, B. Anlar, A. G. Engel

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Forty-two missense, truncation, or splice-site mutations of the acetylcholine receptor (AChR) subunit genes have been reported to date in patients with congenital myasthenic syndromes. Here we report a homozygous mutation, ε-155G→A, in the promoter region of the AChR ε subunit gene that converts the Ets-binding site of the promoter region from CGGAA to CAGAA. The asymptomatic parents and brother are heterozygous and an affected sister is homozygous for ε-155G→A. The Ets-binding site mediates synapse specific expression of the AChR ε subunit gene. An identical G-to-A mutation in the mouse Ets-binding site was previously shown to decrease the binding affinity of the Ets-binding site for the GA binding protein, a transactivating factor for the Ets-binding site, and to reduce the synapse specific expression of the ε subunit. The decreased synaptic expression of the ε subunit readily accounts for the congenital myasthenic phenotype. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)131-135
Number of pages5
JournalNeuromuscular Disorders
Volume9
Issue number3
DOIs
StatePublished - May 1 1999

Keywords

  • Acetylcholine receptor
  • Acetylcholine receptor ε subunit
  • Congenital myasthenic syndromes
  • Ets-binding site
  • GA binding protein
  • MAP kinase
  • Neuregulin
  • erbB receptors

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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