XYLT1 Mutations in Desbuquois Dysplasia Type 2

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2014 Mar 4

PMID 24581741

Citations 55

Authors

Catherine Bui

Celine Huber

Beyhan Tuysuz

Yasemin Alanay

Christine Bole-Feysot

Jules G Leroy

Geert Mortier

Patrick Nitschke

Arnold Munnich

Valerie Cormier-Daire

Affiliations

Soon will be listed here.

Abstract

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.

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