Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE

Ricardo A Maselli, J. Arredondo, O. Cagney, T. Mozaffar, S. Skinner, S. Yousif, Rr Davis, Jeffrey Gregg, M. Sivak, Thomas Konia, K. Thomas, Rl Wollmann

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Mutations in the plectin gene (PLEC1) cause epidermolysis bullosa simplex (EBS), which may associate with muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA). The association of EBS with congenital myasthenic syndrome (CMS) is also suspected to result from PLEC1 mutations. We report here a consanguineous patient with EBS and CMS for whom mutational analysis of PLEC1 revealed a homozygous 36 nucleotide insertion (1506-1507ins36) that results in a reduced expression of PLEC1 mRNA and plectin in the patient muscle. In addition, mutational analysis of CHRNE revealed a homozygous 1293insG, which is a well-known low-expressor receptor mutation. A skin biopsy revealed signs of EBS, and an anconeus muscle biopsy showed signs of a mild myopathy. Endplate studies showed fragmentation of endplates, postsynaptic simplification, and large collections of thread-like mitochondria. Amplitudes of miniature endplate potentials were diminished, but the endplate quantal content was actually increased. The complex phenotype presented here results from mutations in two separate genes. While the skin manifestations are because of the PLEC1 mutation, footprints of mutations in PLEC1 and CHRNE are present at the neuromuscular junction of the patient indicating that abnormalities in both genes contribute to the CMS phenotype.

Original languageEnglish (US)
Pages (from-to)444-451
Number of pages8
JournalClinical Genetics
Issue number5
StatePublished - Nov 2011


  • Congenital myasthenic syndrome
  • Epidermolysis bullosa
  • Neuromuscular junction
  • Plectin

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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