A Connective Tissue Disorder Caused by Mutations of the Lysyl Hydroxylase 3 Gene

Antti M. Salo, Helen Cox, Peter Farndon, Celia Moss, Helen Grindulis, Maija Risteli, Simon P. Robins, Raili Myllyla

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)


Lysyl hydroxylase 3 (LH3, encoded by PLOD3) is a multifunctional enzyme capable of catalyzing hydroxylation of lysyl residues and O-glycosylation of hydroxylysyl residues producing either monosaccharide (Gal) or disaccharide (Glc-Gal) derivatives, reactions that form part of the many posttranslational modifications required during collagen biosynthesis. Animal studies have confirmed the importance of LH3, particularly in biosynthesis of the highly glycosylated type IV and VI collagens, but to date, the functional significance in vivo of this enzyme in man is predominantly unknown. We report here a human disorder of LH3 presenting as a compound heterozygote with recessive inheritance. One mutation dramatically reduced the sugar-transfer activity of LH3, whereas another abrogated lysyl hydroxylase activity; these changes were accompanied by reduced LH3 protein levels in cells. The disorder has a unique phenotype causing severe morbidity as a result of features that overlap with a number of known collagen disorders.

Original languageEnglish
Pages (from-to)495-503
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number4
Early online date2 Oct 2008
Publication statusPublished - 10 Oct 2008


  • early rheumatoid-arthritis
  • collagen cross-linking
  • lysyl-hydroxylase-3 LH3
  • expression
  • identification
  • glycosylation
  • localization
  • progression
  • telopeptide
  • isoforms


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