Get access

COL4A1 mutation in Axenfeld–Rieger anomaly with leukoencephalopathy and stroke

Authors

  • Igor Sibon MD, PhD,

    Corresponding author
    1. Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
    • Department of Neurology, CHU Bordeaux, 33076 Bordeaux Cedex, France
    Search for more papers by this author
    • I.S. and I.C. contributed equally to this work.

  • Isabelle Coupry PhD,

    1. Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
    Search for more papers by this author
    • I.S. and I.C. contributed equally to this work.

  • Patrice Menegon MD,

    1. Centre Hospitalier Universitaire Bordeaux, Service de Neuroradiologie, Hôpital Pellegrin, Bordeaux, France
    Search for more papers by this author
  • Jean-Pierre Bouchet MD,

    1. Cabinet d'Ophtalmologie, Mont de Marsan, Bordeaux, France
    Search for more papers by this author
  • Philippe Gorry MD, PhD,

    1. Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
    2. Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
    Search for more papers by this author
  • Ingrid Burgelin LT,

    1. Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
    Search for more papers by this author
  • Patrick Calvas MD, PhD,

    1. Centre Hospitalier Universitaire Toulouse, Service de Génétique Médicale, Hôpital Purpan, Toulouse, France
    Search for more papers by this author
  • Isabelle Orignac MS,

    1. Centre Hospitalier Universitaire Bordeaux, Département d'Ophtalmologie, Hôpital Pellegrin, Bordeaux, France
    Search for more papers by this author
  • Vincent Dousset MD, PhD,

    1. Centre Hospitalier Universitaire Bordeaux, Service de Neuroradiologie, Hôpital Pellegrin, Bordeaux, France
    Search for more papers by this author
  • Didier Lacombe MD,

    1. Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
    2. Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
    Search for more papers by this author
  • Jean-Marc Orgogozo MD,

    1. Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
    Search for more papers by this author
  • Benoît Arveiler PharmD, PhD,

    1. Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
    2. Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
    Search for more papers by this author
  • Cyril Goizet MD, PhD

    1. Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
    2. Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
    3. Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
    Search for more papers by this author

Abstract

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

Ancillary