Twenty-five novel mutations including duplications in the ATP7A gene

M. P. Moizard, N. Ronce, S. Blesson, E. Bieth, L. Burglen, C. Mignot, I. Mortemousque, N. Marmin, B. Dessay, C. Danesino, F. Feillet, P. Castelnau, A. Toutain, C. Moraine, M. Raynaud

Research output: Contribution to journalArticlepeer-review


Menkes disease (MD) and occipital horn syndrome (OHS) are allelic X-linked recessive copper deficiency disorders resulting from ATP7A gene mutations. MD is a severe condition leading to progressive neurological degeneration and death in early childhood, whereas OHS has a milder phenotype with mainly connective tissue abnormalities. Until now, molecular analyses have revealed only deletions and point mutations in both diseases. This study reports new molecular data in a series of 40 patients referred for either MD or OHS. We describe 23 point mutations (9 missense mutations, 7 splice site variants, 4 nonsense mutations, and 3 small insertions or deletions) and 7 intragenic deletions. Of these, 18 point mutations and 3 deletions are novel. Furthermore, our finding of four whole exon duplications enlarges the mutation spectrum in the ATP7A gene. ATP7A alterations were found in 85% of cases. Of these alterations, two thirds were point mutations and the remaining one third consisted of large rearrangements. We found that 66.6% of point mutations resulted in impaired ATP7A transcript splicing, a phenomenon more frequent than expected. This finding enabled us to confirm the pathogenic role of ATP7A mutations, particularly in missense and splice site variants.

Original languageEnglish
Pages (from-to)243-253
Number of pages11
JournalClinical Genetics
Issue number3
Publication statusPublished - Mar 2011


  • ATP7A
  • Duplication
  • Menkes disease
  • MRNA splicing mutations
  • Occipital horn syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)


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