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

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, epsilon-155G --> A, in the promoter region of the AChR epsilon 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 epislon-155G --> A. The Ets-binding site mediates synapse specific expression of the AChR epsilon 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 epsilon subunit. The decreased synaptic expression of the epsilon subunit readily accounts for the congenital myasthenic phenotype.

• Authors: K Ohno, B Anlar, A G Engel
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 9 Issue 3 Pg. 131-5 (May 1999) ISSN: 0960-8966 [Print] England
• PMID: 10382905 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-ets
• Receptors, Cholinergic
• Transcription Factors
• DNA

Topics

• Adolescent
• Base Sequence
• Binding Sites (drug effects, genetics)
• Child
• DNA (chemistry, genetics)
• DNA Mutational Analysis
• Family Health
• Female
• Gene Expression
• Humans
• Male
• Molecular Sequence Data
• Motor Endplate (genetics)
• Mutation
• Myasthenia Gravis (drug therapy, genetics)
• Pedigree
• Point Mutation
• Promoter Regions, Genetic
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-ets
• Receptors, Cholinergic (genetics, metabolism)
• Sequence Homology, Nucleic Acid
• Syndrome
• Transcription Factors (metabolism)