2. Academic Validation
  3. XYLT1 mutations in Desbuquois dysplasia type 2

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.
Catherine Bui 1,  Céline Huber 1,  Beyhan Tuysuz 2,  Yasemin Alanay 3,  Christine Bole-Feysot 4,  Jules G Leroy 5,  Geert Mortier 6,  Patrick Nitschke 7,  Arnold Munnich 1,  Valérie Cormier-Daire 8
Affiliations

Affiliations

  • 1 Department of Genetics, INSERM U781, Université Paris Descartes- Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades (AP-HP), Paris 75015, France.
  • 2 Department of Pediatric Genetics, Cerrahpasa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
  • 3 Pediatric Genetics Unit, Department of Pediatrics, School of Medicine, Acibadem University, Istanbul 34457, Turkey.
  • 4 Plateforme de Génomique, Fondation IMAGINE, Paris 75015, France.
  • 5 Greenwood Genetic Center, Greenwood, SC 29646, USA.
  • 6 Department of Medical Genetics, Antwerp University Hospital and University of Antwerp, Edegem 2650, Belgium.
  • 7 Plateforme de Bioinformatique, Université Paris Descartes, Paris 75015, France.
  • 8 Department of Genetics, INSERM U781, Université Paris Descartes- Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades (AP-HP), Paris 75015, France. Electronic address: valerie.cormier-daire@inserm.fr.
PMID: 24581741 DOI: 10.1016/j.ajhg.2014.01.020
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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