title: Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome.
abstract: Mutations in the COL4A5 gene, which encodes the a5 chain of type IV collagen, are found in a large fraction of patients with X-linked Alport syndrome. The recently discovered COL4A6, tightly linked and highly homologous to COL4A5, represents a second candidate gene for Alport syndrome. We analyzed 177 Italian Alport syndrome families by Southern blotting using cDNA probes from both COL4A5 and COL4A6. Nine unrelated families, accounting for 5% of the cases, were found to have a rearrangement in COL4A5. No rearrangements were found in COL4A6, with the exception of a deletion encompassing the 5' ends of both COL4A5 and COL4A6 genes in a patient with Alport syndrome and leiomyomatosis. COL4A5 rearrangements were all intragenic and included 1 duplication and 7 deletions. Polymerase chain reaction (PCR) analysis was carried out to characterize deletion and duplication boundaries and to predict the resulting protein abnormality. The two smallest deletions involved a single exon (exons 17 and 40, respectively), while the largest ones spanned exons 1 to 36. The clinical phenotype of patients in whom a rearrangement in COL4A5 was detected was severe, with progression to end-stage renal failure in juvenile age and hypoacusis occurring in most cases. These data have some important implications in the diagnosis of patients with Alport syndrome.
authors.affiliation: Department of Molecular Biology, Policlinico Le Scotte, Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Renieri
authors.forename: L
authors.initials: L
authors.lastname: Galli
authors.forename: A
authors.initials: A
authors.lastname: Grillo
authors.forename: M
authors.initials: M
authors.lastname: Bruttini
authors.forename: T
authors.initials: T
authors.lastname: Neri
authors.forename: P
authors.initials: P
authors.lastname: Zanelli
authors.forename: G
authors.initials: G
authors.lastname: Rizzoni
authors.forename: L
authors.initials: L
authors.lastname: Massella
authors.forename: A
authors.initials: A
authors.lastname: Sessa
authors.forename: M
authors.initials: M
authors.lastname: Meroni
authors.forename: L
authors.initials: L
authors.lastname: Peratoner
authors.forename: P
authors.initials: P
authors.lastname: Riegler
authors.forename: F
authors.initials: F
authors.lastname: Scolari
authors.forename: M
authors.initials: M
authors.lastname: Mileti
authors.forename: M
authors.initials: M
authors.lastname: Giani
authors.forename: M
authors.initials: M
authors.lastname: Cossu
authors.forename: M
authors.initials: M
authors.lastname: Savi
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
authors.forename: M
authors.initials: M
authors.lastname: De Marchi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003094:Collagen / Q000145:classification / Q000235:genetics*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005796:Genes; D006801:Humans; D006822:Hybrid Cells; D007558:Italy / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000209:etiology; D018231:Leiomyomatosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000145:classification / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D014960:X Chromosome / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D003094:Collagen