title: Alport syndrome and diffuse leiomyomatosis: deletions in the 5' end of the COL4A5 collagen gene.
abstract: Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen alpha 5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with diffuse esophageal leiomyomatosis (DL) has been reported in 24 patients, most of them also suffering from congenital cataract. The mode of transmission and the location of the gene(s) involved in this association have not been elucidated. Southern blotting using cDNA probes spanning the whole COL4A5 and a 5' end COL4A5 genomic probe showed that three out of three patients with the DL-AS association had a deletion in the 5' part of the COL4A5 gene extending beyond its 5' end. This indicates that the same gene, COL4A5, is involved in classical AS and in DL-AS and that the transmission of DL-AS is X-linked dominant. These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS.
authors.affiliation: INSERM U192, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Antignac
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Sanak
authors.forename: P
authors.initials: P
authors.lastname: Cochat
authors.forename: B
authors.initials: B
authors.lastname: Roussel
authors.forename: G
authors.initials: G
authors.lastname: Deschênes
authors.forename: F
authors.initials: F
authors.lastname: Gros
authors.forename: B
authors.initials: B
authors.lastname: Knebelmann
authors.forename: M C
authors.initials: MC
authors.lastname: Hors-Cayla
authors.forename: K
authors.initials: K
authors.lastname: Tryggvason
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D003094:Collagen / Q000235:genetics*; D004252:DNA Mutational Analysis; D015342:DNA Probes; D004938:Esophageal Neoplasms / Q000150:complications / Q000235:genetics*; D005091:Exons; D008040:Genetic Linkage; D006801:Humans; D007889:Leiomyoma / Q000150:complications / Q000235:genetics*; D008297:Male; D009394:Nephritis, Hereditary / Q000150:complications / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D014960:X Chromosome
chemical_list: D015342:DNA Probes; D003094:Collagen