XYLT1 Mutations in Desbuquois Dysplasia Type 2

BUI C., HUBER C., Tuysuz B., ALANAY Y., Bole-Feysot C., LEROY J. G., ...More

AMERICAN JOURNAL OF HUMAN GENETICS, vol.94, no.3, pp.405-414, 2014 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 94 Issue: 3
  • Publication Date: 2014
  • Doi Number: 10.1016/j.ajhg.2014.01.020
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.405-414
  • Acibadem Mehmet Ali Aydinlar University Affiliated: Yes


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.