COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps

Plaisier, E. et al. (2007) COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. New England Journal of Medicine, 357(26), pp. 2687-2695. (doi: 10.1056/NEJMoa071906)

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Publisher's URL: http://dx.doi.org/10.1056/NEJMoa071906

Abstract

<i>Background</i>: COL4A3, COL4A4, and COL4A5 are the only collagen genes that have been implicated in inherited nephropathies in humans. However, the causative genes for a number of hereditary multicystic kidney diseases, myopathies with cramps, and heritable intracranial aneurysms remain unknown.<p></p> <i>Methods</i>: We characterized the renal and extrarenal phenotypes of subjects from three families who had an autosomal dominant hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC), which we propose is a syndrome. Linkage studies involving microsatellite markers flanking the COL4A1–COL4A2 locus were performed, followed by sequence analysis of COL4A1 complementary DNA extracted from skin-fibroblast specimens from the subjects.<p></p> <i>Results</i>: We identified three closely located glycine mutations in exons 24 and 25 of the gene COL4A1, which encodes procollagen type IV 1. The clinical renal manifestations of the HANAC syndrome in these families include hematuria and bilateral, large cysts. Histologic analysis revealed complex basement-membrane defects in kidney and skin. The systemic angiopathy of the HANAC syndrome appears to affect both small vessels and large arteries.<p></p> <i>Conclusions</i>: COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Van Agtmael, Dr Tom
Authors: Plaisier, E., Gribouval, O., Alamowitch, S., Mougenot, B., Prost, C., Verpont, M. C., Marro, B., Desmettre, T., Cohen, S. Y., Roullet, E., Dracon, M., Fardeau, M., Van Agtmael, T., Kerjaschki, D., Antignac, C., and Ronco, P.
Subjects:R Medicine > R Medicine (General)
R Medicine > RC Internal medicine
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:New England Journal of Medicine
Publisher:Massachusetts Medical Society
ISSN:0028-4793
ISSN (Online):1533-4406
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
471511Collagen type IV in vascular biologyTom Van AgtmaelMedical Research Council (MRC)G0601268Institute of Cardiovascular and Medical Sciences