Published Online
on March 22, 2007

A more recent version of this article appeared on May 1, 2007

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Submitted on October 10, 2006
Revised on October 24, 2006
Accepted on November 1, 2006

COL4A1 Mutation in a Patient With Sporadic, Recurrent Intracerebral Hemorrhage

Katayoun Vahedi MD^*; Nathalie Kubis MD, PhD; Monique Boukobza MD; Minh Arnoult MD, PhD; Pascale Massin MD; Elisabeth Tournier-Lasserve MD; and Marie-Germaine Bousser MD

From AP-HP, Service de Neurologie (K.V., N.K., M.G.B.), Centre de Référence pour les Maladies Vasculaires Rares du Système Nerveux Central et de la Rétine (K.V., M.B., P.M., E.T.-L., M.G.B.), and Physiologie-Explorations Fonctionnelles (N.K.), Hôpital Lariboisière, Paris; INSERM U689 (N.K.), Université Paris VII, Paris; AP-HP, Service de Neuroradiologie (M.B.), Hôpital Lariboisière; Paris; INSERM U740 (M.A., E.T.-L., M.G.B.), Université Paris VII, Paris; and AP-HP, Service d’Ophthalmologie (P.M.) and Laboratoire de Cytogénétique (E.T.-L.), Hôpital Lariboisière, Paris, France.

^* To whom correspondence should be addressed. E-mail: katayoun.vahedi{at}lrb.aphp.fr.

Background and Purpose--Recently COL4A1, a gene encoding the type IV collagen 1 chain, has been found to be involved in families with autosomal-dominant porencephaly and infantile hemiparesis. In addition to neonatal stroke, some family members had experienced, during adulthood, spontaneous intracerebral hemorrhages (ICHs) and leukoencephalopathy, suggestive of underlying small-vessel disease of the brain. We now report a patient with sporadic, recurrent ICHs and a novel COL4A1 mutation.

Methods--We performed a clinical and genetic study of a 25-year-old-patient with an 8-year history of recurrent ICHs.

Results--This young, normotensive patient with a history of infantile hemiparesis had experienced, since the age of 17, recurrent, spontaneous, deep ICHs occurring during sports activities. He became severely disabled. Brain magnetic resonance imaging showed ventricular enlargement, diffuse white-matter abnormalities, and newly appearing, deep, silent microbleeds. Extensive investigations found no cause. There was no family history of stroke or infantile hemiparesis. A novel COL4A1 mutation (G805R) was identified.

Conclusions--The clinical spectrum of COL4A1 mutations includes recurrent ICHs in association with diffuse leukoencephalopathy in young adults, even in the absence of a family history of infantile hemiparesis or ICH. In addition to birth trauma, anticoagulant use, and head trauma previously reported, sports activities may be a precipitating factor of ICHs in persons with COL4A1 mutations.

Key words: intracerebral hemorrhage • genetics • white matter • young adults

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