title: XYLT1 mutations in Desbuquois dysplasia type 2.
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.
authors.affiliation: Department of Genetics, INSERM U781, Université Paris Descartes- Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades (AP-HP), Paris 75015, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bui
authors.affiliation: Department of Genetics, INSERM U781, Université Paris Descartes- Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades (AP-HP), Paris 75015, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Huber
authors.affiliation: Department of Pediatric Genetics, Cerrahpasa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tuysuz
authors.affiliation: Pediatric Genetics Unit, Department of Pediatrics, School of Medicine, Acibadem University, Istanbul 34457, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Alanay
authors.affiliation: Plateforme de Génomique, Fondation IMAGINE, Paris 75015, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bole-Feysot
authors.affiliation: Greenwood Genetic Center, Greenwood, SC 29646, USA.
authors.forename: Jules G
authors.initials: JG
authors.lastname: Leroy
authors.affiliation: Department of Medical Genetics, Antwerp University Hospital and University of Antwerp, Edegem 2650, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.affiliation: Plateforme de Bioinformatique, Université Paris Descartes, Paris 75015, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Nitschke
authors.affiliation: Department of Genetics, INSERM U781, Université Paris Descartes- Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades (AP-HP), Paris 75015, France.
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.affiliation: 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.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D003241:Consanguinity; D019465:Craniofacial Abnormalities / Q000235:genetics*; D018076:DNA, Complementary / Q000378:metabolism; D004392:Dwarfism / Q000235:genetics*; D059472:Exome; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007593:Joint Instability / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D009999:Ossification, Heterotopic / Q000235:genetics*; D010430:Pentosyltransferases / Q000235:genetics* / Q000378:metabolism; D017689:Polydactyly / Q000235:genetics*; D011509:Proteoglycans / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000097608:UDP Xylose-Protein Xylosyltransferase
chemical_list: D018076:DNA, Complementary; D010430:Pentosyltransferases; D011509:Proteoglycans; D000097608:UDP Xylose-Protein Xylosyltransferase