Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome

Am J Med Genet. 1995 Nov 20;59(3):380-5. doi: 10.1002/ajmg.1320590320.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Chromosomes, Human, Pair 2 / genetics
  • Collagen / classification
  • Collagen / genetics*
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Disease Progression
  • Exons / genetics
  • Female
  • Frameshift Mutation
  • Genes
  • Humans
  • Hybrid Cells
  • Italy / epidemiology
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / etiology
  • Leiomyomatosis / genetics
  • Male
  • Middle Aged
  • Nephritis, Hereditary / classification
  • Nephritis, Hereditary / diagnosis
  • Nephritis, Hereditary / epidemiology
  • Nephritis, Hereditary / genetics*
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Sequence Deletion*
  • X Chromosome / genetics*


  • DNA, Complementary
  • Collagen