COL4A1 mutation in Axenfeld–Rieger anomaly with leukoencephalopathy and stroke
Corresponding Author
Igor Sibon MD, PhD
Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
I.S. and I.C. contributed equally to this work.
Department of Neurology, CHU Bordeaux, 33076 Bordeaux Cedex, FranceSearch for more papers by this authorIsabelle Coupry PhD
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
I.S. and I.C. contributed equally to this work.
Search for more papers by this authorPatrice Menegon MD
Centre Hospitalier Universitaire Bordeaux, Service de Neuroradiologie, Hôpital Pellegrin, Bordeaux, France
Search for more papers by this authorJean-Pierre Bouchet MD
Cabinet d'Ophtalmologie, Mont de Marsan, Bordeaux, France
Search for more papers by this authorPhilippe Gorry MD, PhD
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
Search for more papers by this authorIngrid Burgelin LT
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Search for more papers by this authorPatrick Calvas MD, PhD
Centre Hospitalier Universitaire Toulouse, Service de Génétique Médicale, Hôpital Purpan, Toulouse, France
Search for more papers by this authorIsabelle Orignac MS
Centre Hospitalier Universitaire Bordeaux, Département d'Ophtalmologie, Hôpital Pellegrin, Bordeaux, France
Search for more papers by this authorVincent Dousset MD, PhD
Centre Hospitalier Universitaire Bordeaux, Service de Neuroradiologie, Hôpital Pellegrin, Bordeaux, France
Search for more papers by this authorDidier Lacombe MD
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
Search for more papers by this authorJean-Marc Orgogozo MD
Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
Search for more papers by this authorBenoît Arveiler PharmD, PhD
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
Search for more papers by this authorCyril Goizet MD, PhD
Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
Search for more papers by this authorCorresponding Author
Igor Sibon MD, PhD
Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
I.S. and I.C. contributed equally to this work.
Department of Neurology, CHU Bordeaux, 33076 Bordeaux Cedex, FranceSearch for more papers by this authorIsabelle Coupry PhD
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
I.S. and I.C. contributed equally to this work.
Search for more papers by this authorPatrice Menegon MD
Centre Hospitalier Universitaire Bordeaux, Service de Neuroradiologie, Hôpital Pellegrin, Bordeaux, France
Search for more papers by this authorJean-Pierre Bouchet MD
Cabinet d'Ophtalmologie, Mont de Marsan, Bordeaux, France
Search for more papers by this authorPhilippe Gorry MD, PhD
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
Search for more papers by this authorIngrid Burgelin LT
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Search for more papers by this authorPatrick Calvas MD, PhD
Centre Hospitalier Universitaire Toulouse, Service de Génétique Médicale, Hôpital Purpan, Toulouse, France
Search for more papers by this authorIsabelle Orignac MS
Centre Hospitalier Universitaire Bordeaux, Département d'Ophtalmologie, Hôpital Pellegrin, Bordeaux, France
Search for more papers by this authorVincent Dousset MD, PhD
Centre Hospitalier Universitaire Bordeaux, Service de Neuroradiologie, Hôpital Pellegrin, Bordeaux, France
Search for more papers by this authorDidier Lacombe MD
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
Search for more papers by this authorJean-Marc Orgogozo MD
Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
Search for more papers by this authorBenoît Arveiler PharmD, PhD
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
Search for more papers by this authorCyril Goizet MD, PhD
Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France
Université Victor Segalen Bordeaux 2, Laboratoire de Génétique Humaine, Développement et Cancer, Bordeaux, France
Centre Hospitalier Universitaire Bordeaux, Service de Génétique Médicale, Hôpital Pellegrin-enfants, Bordeaux, France
Search for more papers by this authorAbstract
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
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