• Emmanuelle Plaisier, Olivier Gribouval, Sonia Alamowitch, Béatrice Mougenot, Catherine Prost, Marie Christine Verpont, Béatrice Marro, Thomas Desmettre, Salomon Yves Cohen, Etienne Roullet, Michel Dracon, Michel Fardeau, Tom Van Agtmael, Dontscho Kerjaschki, Corinne Antignac, and Pierre Ronco.
• INSERM Unité 702, Université Pierre et Marie Curie, Paris 6, Unités Mixtes de Recherche Scientifique 702, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, France. emmanuelle.plaisier@tnn.aphp.fr
• N. Engl. J. Med. 2007 Dec 27; 357 (26): 2687-95.

BackgroundCOL4A3, 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.MethodsWe 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.ResultsWe identified three closely located glycine mutations in exons 24 and 25 of the gene COL4A1, which encodes procollagen type IV alpha1. 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.ConclusionsCOL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps.Copyright 2007 Massachusetts Medical Society.

29 keywords...

hide…