Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IV α5 chain

Kidney Int. 2014 May;85(5):1208-13. doi: 10.1038/ki.2013.479. Epub 2013 Dec 4.

Abstract

X-linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain (α5(IV)). Complete absence of α5(IV) in the renal basal membrane is considered a pathological characteristic in male patients; however, positive α5(IV) staining has been found in over 20% of patients. We retrospectively studied 52 genetically diagnosed male X-linked Alport syndrome patients to evaluate differences in clinical characteristics and renal outcomes between 15 α5(IV)-positive and 37 α5(IV)-negative patients. Thirteen patients in the α5(IV)-positive group had non-truncating mutations consisting of nine missense mutations, three in-frame deletions, and one splice-site mutation resulting in small in-frame deletions of transcripts. The remaining two showed somatic mutations with mosaicism. Missense mutations in the α5(IV)-positive group were more likely to be located before exon 25 compared with missense mutations in the α5(IV)-negative group. Furthermore, urinary protein levels were significantly lower and the age at onset of end-stage renal disease was significantly higher in the positive group than in the negative group. These results help to clarify the milder clinical manifestations and molecular characteristics of male X-linked Alport syndrome patients expressing the α5(IV) chain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Biopsy
  • Child
  • Child, Preschool
  • Collagen Type IV / analysis
  • Collagen Type IV / genetics*
  • Disease Progression
  • Exons
  • Genetic Predisposition to Disease
  • Glomerular Basement Membrane / chemistry*
  • Glomerular Basement Membrane / pathology
  • Humans
  • Immunohistochemistry
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / metabolism
  • Male
  • Mosaicism
  • Mutation*
  • Mutation, Missense
  • Nephritis, Hereditary / diagnosis
  • Nephritis, Hereditary / genetics*
  • Nephritis, Hereditary / metabolism
  • Phenotype
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Sequence Deletion
  • Severity of Illness Index
  • Time Factors
  • Young Adult

Substances

  • COL4A5 protein, human
  • Collagen Type IV