COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke

Ann Neurol. 2007 Aug;62(2):177-84. doi: 10.1002/ana.21191.


Objective: Several hereditary ischemic small-vessel diseases of the brain have been reported during the last decade. Some of them have ophthalmological, mainly retinal, manifestations. Herein, we report on a family affected by vascular leukoencephalopathy and variable abnormalities of the anterior chamber of the eye.

Methods: After the occurrence of a small, deep infarct associated with white matter lesions in a patient with a medical history of congenital cataract and amblyopia, we conducted clinical and neuroradiological investigations in 10 of her relatives.

Results: Diffuse leukoencephalopathy associated with ocular malformations of the Axenfeld-Rieger type was observed in five individuals. Familial genetic analyses led to the identification of a novel missense mutation in the COL4A1 gene, p.G720D, which cosegregates with the disease.

Interpretation: Our data corroborate previous observations demonstrating the role of COL4A1 in cerebral microangiopathy and expand the phenotypic spectrum associated with mutations in this gene. We delineate a novel association between the Axenfeld-Rieger anomaly and leukoencephalopathy and stroke. Ann Neurol 2007.

Publication types

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

MeSH terms

  • Adult
  • Anterior Eye Segment / abnormalities*
  • Aspartic Acid
  • Autoantigens / genetics*
  • Brain Diseases / diagnosis
  • Brain Diseases / genetics*
  • Child
  • Collagen Type IV / genetics*
  • Eye Abnormalities / genetics*
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Glycine
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Pedigree
  • Stroke / diagnosis
  • Stroke / genetics*


  • Autoantigens
  • Collagen Type IV
  • type IV collagen alpha3 chain
  • Aspartic Acid
  • Glycine