Similar splicing mutations of the Menkes/mottled copper-transporting ATPase gene in occipital horn syndrome and the blotchy mouse

Am J Hum Genet. 1995 Mar;56(3):570-6.


The connective-tissue disorder occipital horn syndrome (OHS) is hypothesized to be allelic to Menkes disease. The two diseases have different clinical presentations but have a similar abnormality of copper transport. Mice hemizygous for the blotchy allele of the X-linked mottled locus have similar connective-tissue defects as OHS and may represent a mouse model of this disease. We have analyzed the Menkes/mottled copper-transporting ATPase in these two potentially homologous disorders and have identified similar splicing mutations in both. Some expression of normal mRNA was detectable by reverse transcription-PCR in the mutant tissues. These findings contrast with the more debilitating mutations observed in Menkes disease and suggest that low amounts of an otherwise normal protein product could result in the relatively mild phenotype of OHS and of the blotchy mouse.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adolescent
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Cation Transport Proteins*
  • Copper / blood
  • Copper-Transporting ATPases
  • Cutis Laxa / genetics*
  • DNA Mutational Analysis
  • Exons
  • Humans
  • Male
  • Mice
  • Mice, Neurologic Mutants / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • RNA Splicing*
  • Recombinant Fusion Proteins*
  • Syndrome


  • Atp7a protein, mouse
  • Carrier Proteins
  • Cation Transport Proteins
  • Recombinant Fusion Proteins
  • Copper
  • Adenosine Triphosphatases
  • ATP7A protein, human
  • Copper-Transporting ATPases

Associated data

  • GENBANK/U03434