Aberrant splicing of the COL4A5 gene in patients with Alport syndrome

Hum Mol Genet. 1994 Feb;3(2):317-22. doi: 10.1093/hmg/3.2.317.


A variety of mutations have been identified in the X-linked type IV collagen alpha 5 chain (COL4A5) gene in patients with Alport syndrome. A substantial number of these mutations were predicted to have an effect on RNA splicing. For 4 such mutations in our group of patients the effect of the DNA mutation on the COL4A5 mRNA structure and stability was analysed. An alteration of the invariant splice acceptor site of intron 41 resulted in a shift of the actual splicing to either a cryptic splice site within exon 42 or the normal splice site in the next intron. A single base substitution of the final nucleotide of exon 48 resulted in the removal of the entire exon. Two frameshift mutations, a 10 basepair duplication in exon 49 and a single base deletion in exon 41, were incorporated in the mRNA as such and resulted in a stretch of missense codons terminated by a premature stop codon. Exon skipping was occasionally observed in these samples, but not reproducibly in every experiment. In healthy controls exon skipping was never detected. Analysis of female carriers revealed that in only one case was the stability of the mutated mRNA reduced in comparison with the normal transcript. The extent to which the non-collagenous domain was predicted to be deleted correlated with the severeness of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Collagen / biosynthesis
  • Collagen / chemistry
  • Collagen / classification
  • Collagen / genetics*
  • Exons
  • Female
  • Frameshift Mutation
  • Gene Expression Regulation
  • Heterozygote
  • Humans
  • Introns
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Nephritis, Hereditary / genetics*
  • Polymerase Chain Reaction
  • RNA Splicing*
  • X Chromosome


  • Collagen