Published online before print January 4, 2007, doi: 10.1161/01.STR.0000254710.32761.44
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2007;38:216.)
© 2007 American Heart Association, Inc.
Advances in Stroke 2006 |
Update on the Genetics of Stroke and Cerebrovascular Disease 2006
From the Neurologische Klinik (M.D.), Klinikum Großhadern, Ludwig-Maximilians-Universität, München, Germany; and the Blackburn Cardiovascular Genetics Laboratory (R.A.H.), Robarts Research Institute, London, Ontario, Canada.
Correspondence to Martin Dichgans, MD, Neurologische Klinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, Marchioninistrasse 15, München, Germany D-81377. E-mail martin.dichgans@med.uni-muenchen.de
Key Words: association • COL4A1 • Genetics • PDE4D • stroke • white matter
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The last year has again seen several advances in the genetics of cerebrovascular disease covering a spectrum of disorders ranging from small vessel disease to intracranial aneurysms to ischemic stroke.
Collagen Type IV
1 and Small Vessel Disease
A key discovery was the identification of collagen type IV 1 (COL4A1) mutations in families with cerebral small vessel disease.1,2 Col4a1 was initially identified as the causative gene in a mouse mutant with perinatal cerebral hemorrhage and porencephalopathy.1 Heterozygous (Col4a1+/
40) mice develop recurrent hemorrhages in the basal ganglia—the typical site of intracerebral hemorrhage in hypertensive patients. Subsequent analysis of affected family members with porencephalopathy and cerebral small vessel disease revealed several mutations in the human COL4A1 gene.1–3
Type IV collagens are an integral component of the vascular basement membrane. COL4A1 and COL4A2, the most abundant type IV collagens, form hetero-trimers. The triple helix domain contains repeated glycine-proline-X motifs, which are critical for helix formation during collagen assembly. Most identified mutations involve glycine residues within such motifs. It was therefore hypothesized that COL4A1 mutations interfere with triple helix formation or heterotrimer secretion; in fact, there is evidence from Col4a1+/40 embryonic tissue that mutations inhibit collagen secretion into the basement membrane. Ultrastructural abnormalities in capillaries from COL4A1 mutation carriers indicate disordered basement membrane assembly.
The phenotypic spectrum associated with COL4A1 mutations is broad and strongly connected to small vessel disease. Key features include leukoencephalopathy, microhemorrhages, and clinically overt hemorrhage. The structural compromise of small blood vessels is illustrated by the fact that birth trauma, brain trauma, and oral anticoagulants may
Related Articles:
Stroke 2007 38: 395-397.
Stroke 2007 38: 241-244.
Stroke 2007 38: 232-234.
Stroke 2007 38: 222-224.
Stroke 2007 38: 219-221.
Stroke 2007 38: 238-240.
Stroke 2007 38: 229-231.
Stroke 2007 38: 235-237.
Stroke 2007 38: 225-228.
Stroke 2007 38: 214-215.
Stroke 2007 38: 245-248.
This article has been cited by other articles:
 |
|
 |
|
  H. Ding, Y. Xu, X. Wang, Q. Wang, L. Zhang, Y. Tu, J. Yan, W. Wang, R. Hui, C.-Y. Wang, et al. 9p21 is a Shared Susceptibility Locus Strongly for Coronary Artery Disease and Weakly for Ischemic Stroke in Chinese Han Population Circ Cardiovasc Genet, August 1, 2009; 2(4): 338 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Talbot The study of rare diseases: butterfly collecting or an entree to understanding common conditions? Practical Neurology, August 1, 2007; 7(4): 210 - 211. [Full Text] [PDF]
|
|