COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke.
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.


CONCLUSIONS
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.
Sibon
Igor
I
Centre Hospitalier Universitaire Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, Bordeaux, France. igor.sibon@chu-bordeaux.fr
Coupry
Isabelle
I
Menegon
Patrice
P
Bouchet
Jean-Pierre
JP
Gorry
Philippe
P
Burgelin
Ingrid
I
Calvas
Patrick
P
Orignac
Isabelle
I
Dousset
Vincent
V
Lacombe
Didier
D
Orgogozo
Jean-Marc
JM
Arveiler
Benoît
B
Goizet
Cyril
C
D000328:Adult; D000869:Anterior Eye Segment / Q000002:abnormalities*; D001224:Aspartic Acid; D001324:Autoantigens / Q000235:genetics*; D001927:Brain Diseases / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D024141:Collagen Type IV / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005998:Glycine; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D020521:Stroke / Q000175:diagnosis / Q000235:genetics*
D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain; D001224:Aspartic Acid; D005998:Glycine