title: Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis.
abstract: Desbuquois dysplasia (DD) is characterized by antenatal and postnatal short stature, multiple dislocations, and advanced carpal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. We have identified mutations in calcium activated nucleotidase 1 gene (CANT1) in DD type 1. Recently, CANT1 mutations have been reported in the Kim variant of DD, characterized by short metacarpals and elongated phalanges. DD has overlapping features with spondyloepiphyseal dysplasia with congenital joint dislocations (SDCD) due to Carbohydrate (chondroitin 6) Sulfotransferase 3 (CHST3) mutations. We screened CANT1 and CHST3 in 38 DD cases (6 type 1 patients, 1 Kim variant, and 31 type 2 patients) and found CANT1 mutations in all DD type 1 cases, the Kim variant and in one atypical DD type 2 expanding the clinical spectrum of hand anomalies observed with CANT1 mutations. We also identified in one DD type 2 case CHST3 mutation supporting the phenotype overlap with SDCD. To further define function of CANT1, we studied proteoglycan synthesis in CANT1 mutated patient fibroblasts, and found significant reduced GAG synthesis in presence of β-D-xyloside, suggesting that CANT1 plays a role in proteoglycan metabolism.
authors.affiliation: Departement de Génétique, INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Nizon
authors.forename: Céline
authors.initials: C
authors.lastname: Huber
authors.forename: Fabio
authors.initials: F
authors.lastname: De Leonardis
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Merrina
authors.forename: Antonella
authors.initials: A
authors.lastname: Forlino
authors.forename: Mélanie
authors.initials: M
authors.lastname: Fradin
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tuysuz
authors.forename: Bassam Y
authors.initials: BY
authors.lastname: Abu-Libdeh
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Alanay
authors.forename: Beate
authors.initials: B
authors.lastname: Albrecht
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
authors.forename: Sarenur Yilmaz
authors.initials: SY
authors.lastname: Basaran
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: Julie
authors.initials: J
authors.lastname: Désir
authors.forename: Harinder
authors.initials: H
authors.lastname: Gill
authors.forename: Marie T
authors.initials: MT
authors.lastname: Greally
authors.forename: Erkan
authors.initials: E
authors.lastname: Koparir
authors.forename: Merel C
authors.initials: MC
authors.lastname: van Maarle
authors.forename: Sara
authors.initials: S
authors.lastname: MacKay
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.forename: Jenny
authors.initials: J
authors.lastname: Morton
authors.forename: David
authors.initials: D
authors.lastname: Sillence
authors.forename: Catheline
authors.initials: C
authors.lastname: Vilain
authors.forename: Ian
authors.initials: I
authors.lastname: Young
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Carine
authors.initials: C
authors.lastname: Le Goff
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D002478:Cells, Cultured; D002850:Chromatography, Gel; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000378:metabolism; D004392:Dwarfism / Q000235:genetics / Q000378:metabolism; D006027:Glycosides / Q000378:metabolism; D006801:Humans; D007593:Joint Instability / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009708:Nucleotidases / Q000235:genetics / Q000378:metabolism*; D009999:Ossification, Heterotopic / Q000235:genetics / Q000378:metabolism; D017689:Polydactyly / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases
chemical_list: D006027:Glycosides; D009708:Nucleotidases; D011509:Proteoglycans; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C010807:xylosides; C551404:CANT1 protein, human