A new mutation in gjc2 associated with subclinical leukodystrophy

Charles K. Abrams, Rafael Flores-Obando, Steven S. Scherer, Sarah Wong, Mona M. Freidin, Eleonora Lamantea, Laura Farina, Vidmer Scaioli, Davide Pareyson, Ettore Salsano

Research output: Contribution to journalArticlepeer-review


Recessive mutations in GJC2, the geneencoding connexin 47 (Cx47), cause Pelizaeus-Merzbacher-like disease type 1, a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype--hereditary spastic paraplegia type 44. Here, we present evidence that a novel Arg98Leu mutation causes an even milder phenotype--a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady-state junctional conductance-junctional voltage (Gj-Vj) relations differed only slightly from those for wild-type Cx47. Our data suggest that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes.

Original languageEnglish
Pages (from-to)1929-1938
Number of pages10
JournalJournal of Neurology
Issue number1
Publication statusPublished - 2014


  • Connexin 47
  • Gap junction
  • Hereditary spastic paraplegia type 44 (SPG44)
  • Pelizaeus-Merzbacher-like disease type 1 (PMLD1)

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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