Alport syndrome associated with diffuse leiomyomatosis: COL4A5-COL4A6 deletion associated with a mild form of Alport nephropathy.
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.
Mothes
Henning
H
Department of General and Visceral Surgery, Friedrich-Schiller-University Jena, Bachstrasse 18, D-07740 Jena, Germany. Henning.mothes@med.uni-jena.de
Heidet
Laurence
L
Arrondel
Christelle
C
Richter
Konrad Klaus
KK
Thiele
Mariana
M
Patzer
Ludwig
L
Sado
Yoshikazu
Y
Gubler
Marie-Claire
MC
Antignac
Corinne
C
Scheele
Johannes
J
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
D024141:Collagen Type IV; D004247:DNA