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COL4A1 mutation in Axenfeld–Rieger anomaly with leukoencephalopathy and stroke
Author(s) -
Sibon Igor,
Coupry Isabelle,
Menegon Patrice,
Bouchet JeanPierre,
Gorry Philippe,
Burgelin Ingrid,
Calvas Patrick,
Orignac Isabelle,
Dousset Vincent,
Lacombe Didier,
Orgogozo JeanMarc,
Arveiler Benoît,
Goizet Cyril
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21191
Subject(s) - leukoencephalopathy , missense mutation , microangiopathy , vascular anomaly , medicine , stroke (engine) , pathology , ophthalmology , disease , mutation , genetics , biology , gene , surgery , diabetes mellitus , mechanical engineering , engineering , endocrinology
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