Browsing by Author "Nitschke, Patrick"

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    XYLT1 Mutations in Desbuquois Dysplasia Type 2
    (CELL PRESS, 2014-01-01) Bui, Catherine; Huber, Celine; Tuysuz, Beyhan; Alanay, Yasemin; Bole-Feysot, Christine; Leroy, Jules G.; Mortier, Geert; Nitschke, Patrick; Munnich, Arnold; Cormier-Daire, Valerie
    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.