Substitution of arginine for glycine 325 in the collagen alpha 5 (IV) chain associated with X-linked Alport syndrome: characterization of the mutation by direct sequencing of PCR-amplified lymphoblast cDNA fragments

Am J Hum Genet. 1992 Jul;51(1):135-42.


A large kindred with adult-type X-linked Alport syndrome was studied with regard to a defect in the recently described COL4A5 collagen gene. Southern blot analysis with COL4A5 cDNA probes showed loss of a MspI restriction site. Direct sequencing of cDNA amplified from lymphoblast mRNA demonstrated a single-base substitution converting a glycine codon to arginine at position 325 in the alpha 5 chain of type IV collagen. The triple-helical collagenous domain of alpha 5(IV), characterized by a Gly-X-Y repeat sequence, is interrupted 22 times by noncollagenous sequences. The mutation creates an additional interruption in the Gly-X-Y repeat motif, between interruptions 4 and 5. It is interesting that such glycine substitutions inside the COL1A1 or COL1A2 genes have been associated with many cases of osteogenesis imperfecta. This gly325-to-arg substitution presumably alters the triple-helix formation, and, in turn, modifies the ultrastructural and functional characteristics of the type IV collagen network inside the glomerular basement membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Arginine
  • Base Sequence
  • Collagen / chemistry*
  • Collagen / genetics
  • Deoxyribonuclease HpaII
  • Deoxyribonucleases, Type II Site-Specific
  • Female
  • Gene Library
  • Genetic Linkage
  • Glycine
  • Humans
  • Lymphocytes
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Nephritis, Hereditary / genetics*
  • Pedigree
  • Polymerase Chain Reaction
  • X Chromosome*


  • Collagen
  • Arginine
  • Deoxyribonuclease HpaII
  • Deoxyribonucleases, Type II Site-Specific
  • Glycine