A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia

Hum Mutat. 2012 Feb;33(2):351-4. doi: 10.1002/humu.21650. Epub 2011 Dec 8.


Autosomal recessive ataxias are heterogeneous group of disorders characterized by cerebellar atrophy and peripheral sensorimotor neuropathy. Molecular characterization of this group of disorders identified a number of genes contributing to these overlapping phenotypes. Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive form of ataxia caused by mutations in the SETX gene. We report on a consanguineous family with autosomal recessive inheritance and clinical characteristics of AOA2, and no mutations in the SETX gene. We mapped the AOA locus in this family to chromosome 17p12-p13. Sequencing of all genes in the refined region identified a homozygous missense mutation in PIK3R5 that was absent in 477 normal controls. Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Apraxias / diagnosis
  • Apraxias / genetics*
  • Ataxia / diagnosis
  • Ataxia / genetics*
  • Ataxia Telangiectasia / diagnosis
  • Ataxia Telangiectasia / genetics*
  • Brain / pathology
  • Cerebellar Ataxia / congenital
  • Class Ib Phosphatidylinositol 3-Kinase / genetics*
  • Consanguinity
  • DNA Helicases
  • Female
  • Gene Order
  • Genetic Linkage
  • Homozygote
  • Humans
  • Hypoalbuminemia / diagnosis
  • Hypoalbuminemia / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Multifunctional Enzymes
  • Mutation, Missense*
  • Pedigree
  • Phenotype
  • Phosphatidylinositol 3-Kinases / genetics*
  • RNA Helicases / genetics
  • Sibling Relations
  • Young Adult


  • Multifunctional Enzymes
  • Class Ib Phosphatidylinositol 3-Kinase
  • SETX protein, human
  • DNA Helicases
  • RNA Helicases

Supplementary concepts

  • Early-onset ataxia with oculomotor apraxia and hypoalbuminemia