title: Alport syndrome associated with diffuse leiomyomatosis: COL4A5-COL4A6 deletion associated with a mild form of Alport nephropathy.
abstract: BACKGROUND
  The X-linked Alport syndrome (AS) is an inherited nephropathy due to mutations in the COL4A5 gene, encoding the alpha5 chain of type IV collagen, a major component of the glomerular basement membrane (GBM). Here, we report a new kindred with the rare association of X-linked AS and diffuse leiomyomatosis (DL), which is a tumourous process involving smooth muscle cells of the oesophagus, the tracheobronchial tree and, in females, the genital tract. For this syndrome, an almost constant association of large COL4A5 rearrangements with a severe juvenile form of nephropathy has been described for male patients.
  
  
  METHODS
  DNA rearrangement at the COL4A5-COL4A6 locus was studied in several members of this family using polymerase chain reaction and pulsed field gel electrophoresis. Furthermore, immunohistochemical staining of tumour and skin samples was performed.
  
  
  RESULTS
  The affected patients in this family carry a 120 kb deletion by which the COL4A5 exon 1 and COL4A6 exons 1, 1', and 2 are removed. Immunohistochemical investigation of a skin biopsy of an affected male patient confirmed the absence of both the alpha5 and the alpha6 chains of type IV collagen in the basement membrane of the skin. Surprisingly, both affected male patients had a rather mild renal phenotype.
  
  
  CONCLUSIONS
  This report shows that, contrary to what has been reported to date, patients suffering from AS associated with DL can be associated with a late onset renal failure (adult) form of nephropathy.
authors.affiliation: Department of General and Visceral Surgery, Friedrich-Schiller-University Jena, Bachstrasse 18, D-07740 Jena, Germany. Henning.mothes@med.uni-jena.de
authors.forename: Henning
authors.initials: H
authors.lastname: Mothes
authors.forename: Laurence
authors.initials: L
authors.lastname: Heidet
authors.forename: Christelle
authors.initials: C
authors.lastname: Arrondel
authors.forename: Konrad Klaus
authors.initials: KK
authors.lastname: Richter
authors.forename: Mariana
authors.initials: M
authors.lastname: Thiele
authors.forename: Ludwig
authors.initials: L
authors.lastname: Patzer
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Johannes
authors.initials: J
authors.lastname: Scheele
mesh_terms: D000328:Adult; D024141:Collagen Type IV / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000209:etiology*; D007680:Kidney Neoplasms / Q000209:etiology*; D018231:Leiomyomatosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000150:complications* / Q000235:genetics / Q000473:pathology
chemical_list: D024141:Collagen Type IV; D004247:DNA