XYLT1 mutations in Desbuquois dysplasia type 2.

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. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Citation

Catherine Bui, Céline Huber, Beyhan Tuysuz, Yasemin Alanay, Christine Bole-Feysot, Jules G Leroy, Geert Mortier, Patrick Nitschke, Arnold Munnich, Valérie Cormier-Daire. XYLT1 mutations in Desbuquois dysplasia type 2. American journal of human genetics. 2014 Mar 06;94(3):405-14

Mesh Tags

Substances

PMID: 24581741

search → result