New ATP8A2 gene mutations associated with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy

Neurogenetics. 2016 Oct;17(4):259-263. doi: 10.1007/s10048-016-0496-y. Epub 2016 Sep 28.

Abstract

We report the clinical and biochemical findings from two unrelated patients who presented with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. Whole exome sequencing (WES) uncovered a homozygous mutation in the ATP8A2 gene (NM_016529:c.1287G > T, p.K429N) in one patient and compound heterozygous mutations (c.1630G > C, p.A544P and c.1873C > T, p.R625W) in the other. Only one haploinsufficiency case and a family with a homozygous mutation in ATP8A2 gene (c.1128C > G, p.I376M) have been described so far, with phenotypes that differed slightly from the patients described herein. In conclusion, our data expand both the genetic and phenotypic spectrum associated with ATP8A2 gene mutations.

Keywords: ATP8A2; Chorea; Encephalopathy; Optic atrophy; Severe hypotonia; Wes.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Brain Diseases / complications
  • Brain Diseases / genetics*
  • Child
  • Child, Preschool
  • Chorea / complications
  • Chorea / genetics*
  • Exome Sequencing
  • Female
  • Homozygote
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / genetics*
  • Muscle Hypotonia / complications
  • Muscle Hypotonia / genetics*
  • Mutation*
  • Optic Atrophy / complications
  • Optic Atrophy / genetics*
  • Pedigree
  • Phospholipid Transfer Proteins / genetics*
  • Syndrome

Substances

  • Phospholipid Transfer Proteins
  • Adenosine Triphosphatases
  • ATP8A2 protein, human