A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome

Antoni Barrientos, Víctor Volpini, Jordi Casademont, David Genís, Josep Maria Manzanares, Isidre Ferrer, Jordi Corral, Francesc Cardellach, Alvaro Urbano-Márquez, Xavier P. Estivill, Virginia Nunes

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Abstract

Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at θ = 0 (P < 0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.

Original languageEnglish
Pages (from-to)1570-1576
Number of pages7
JournalJournal of Clinical Investigation
Volume97
Issue number7
Publication statusPublished - 1 Apr 1996
Externally publishedYes

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Keywords

  • autosomal recessive inheritance
  • DIDMOAD
  • linkage
  • neurodegenerative disease
  • OXPHOS

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Barrientos, A., Volpini, V., Casademont, J., Genís, D., Manzanares, J. M., Ferrer, I., Corral, J., Cardellach, F., Urbano-Márquez, A., Estivill, X. P., & Nunes, V. (1996). A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome. Journal of Clinical Investigation, 97(7), 1570-1576.