title: COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps.
authors.affiliation: 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
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Plaisier
authors.forename: Olivier
authors.initials: O
authors.lastname: Gribouval
authors.forename: Sonia
authors.initials: S
authors.lastname: Alamowitch
authors.forename: Béatrice
authors.initials: B
authors.lastname: Mougenot
authors.forename: Catherine
authors.initials: C
authors.lastname: Prost
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Verpont
authors.forename: Béatrice
authors.initials: B
authors.lastname: Marro
authors.forename: Thomas
authors.initials: T
authors.lastname: Desmettre
authors.forename: Salomon Yves
authors.initials: SY
authors.lastname: Cohen
authors.forename: Etienne
authors.initials: E
authors.lastname: Roullet
authors.forename: Michel
authors.initials: M
authors.lastname: Dracon
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
authors.forename: Tom
authors.initials: T
authors.lastname: Van Agtmael
authors.forename: Dontscho
authors.initials: D
authors.lastname: Kerjaschki
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001485:Basement Membrane / Q000473:pathology; D024141:Collagen Type IV / Q000235:genetics*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006417:Hematuria / Q000235:genetics; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000473:pathology; D008297:Male; D009120:Muscle Cramp / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome; D014652:Vascular Diseases / Q000235:genetics*
chemical_list: D024141:Collagen Type IV