XYLT1 mutations in Desbuquois dysplasia type 2

Am J Hum Genet. 2014 Mar 6;94(3):405-14. doi: 10.1016/j.ajhg.2014.01.020. Epub 2014 Feb 27.


Desbuquois dysplasia (DBQD) is a severe condition characterized by short stature, joint laxity, and advanced carpal ossification. Based on the presence of additional hand anomalies, we have previously distinguished DBQD type 1 and identified CANT1 (calcium activated nucleotidase 1) mutations as responsible for DBQD type 1. We report here the identification of five distinct homozygous xylosyltransferase 1 (XYLT1) mutations in seven DBQD type 2 subjects from six consanguineous families. Among the five mutations, four were expected to result in loss of function and a drastic reduction of XYLT1 cDNA level was demonstrated in two cultured individual fibroblasts. Because xylosyltransferase 1 (XT-I) catalyzes the very first step in proteoglycan (PG) biosynthesis, we further demonstrated in the two individual fibroblasts a significant reduction of cellular PG content. Our findings of XYLT1 mutations in DBQD type 2 further support a common physiological basis involving PG synthesis in the multiple dislocation group of disorders. This observation sheds light on the key role of the XT-I during the ossification process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bone and Bones / metabolism
  • Child
  • Consanguinity
  • Craniofacial Abnormalities / genetics*
  • DNA, Complementary / metabolism
  • Dwarfism / genetics*
  • Exome
  • Female
  • Fibroblasts / metabolism
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Joint Instability / genetics*
  • Male
  • Microsatellite Repeats / genetics
  • Mutation*
  • Ossification, Heterotopic / genetics*
  • Pentosyltransferases / genetics*
  • Pentosyltransferases / metabolism
  • Polydactyly / genetics*
  • Proteoglycans / metabolism
  • Sequence Analysis, DNA
  • UDP Xylose-Protein Xylosyltransferase


  • DNA, Complementary
  • Proteoglycans
  • Pentosyltransferases

Supplementary concepts

  • Desbuquois syndrome