Hemorrhagic cerebral small vessel disease caused by a novel mutation in 3′ UTR of collagen type IV alpha 1

Abstract

Collagen type IV alpha 1 (COL4A1) is a major basement membrane component. Haploinsufficiency mutations in COL4A1 interrupt the basement membrane integrity, causing hemorrhagic stroke.1 Recently, mutations causing overproduction of COL4A1 mRNA have been identified in patients with cerebral small vessel disease (CSVD), including in members of families with pontine autosomal dominant microangiopathy with leukoencephalopathy2 and multi-infarct dementia of Swedish type.3 These mutations are located in the 3′ untranslated region (UTR) of COL4A1 and disrupt the binding of miR-29 to the 3′UTR of COL4A1 .2 Both diseases are characterized by leukoencephalopathy, multiple microbleeds (MBs), and multiple lacunar infarctions (LIs) with pontine involvements.2–4 However, among these patients, only case of hemorrhagic stroke was reported.5 Thus, it is unclear whether these mutations, which increase the amount of normal COL4A1, cause hemorrhagic stroke. Here, we report a patient with hemorrhagic stroke with a novel mutation in the 3′UTR of COL4A1 .