A silent nucleotide substitution in the ATP7A gene in a child with Menkes disease

Mol Genet Metab. 2013 Dec;110(4):490-2. doi: 10.1016/j.ymgme.2013.09.012. Epub 2013 Sep 24.

Abstract

We present a case of classical Menkes disease (MD) due to a novel "silent" substitution in the ATP7A gene; c.2781G>A (p.K927K). The affected nucleotide is the last nucleotide in exon 13, and affects mRNA splicing. Transcripts missing exon 13; and transcripts missing exons 11, 12 and 13 in addition to a very small amount of normal spliced ATP7A transcripts were expressed. This is the first report of a synonymous ATP7A substitution being responsible for MD.

Keywords: ATP7A; Genotype–phenotype; Menkes disease; Silent mutation.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Cation Transport Proteins / genetics*
  • Copper-Transporting ATPases
  • Exons
  • Genetic Association Studies
  • Humans
  • Male
  • Menkes Kinky Hair Syndrome / genetics*
  • Menkes Kinky Hair Syndrome / pathology
  • Mutation
  • RNA Splicing / genetics*

Substances

  • Cation Transport Proteins
  • Adenosine Triphosphatases
  • ATP7A protein, human
  • Copper-Transporting ATPases