1. Academic Validation
  2. Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis

Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis

  • Hum Mutat. 2012 Aug;33(8):1261-6. doi: 10.1002/humu.22104.
Mathilde Nizon 1 Céline Huber Fabio De Leonardis Rodolphe Merrina Antonella Forlino Mélanie Fradin Beyhan Tuysuz Bassam Y Abu-Libdeh Yasemin Alanay Beate Albrecht Lihadh Al-Gazali Sarenur Yilmaz Basaran Jill Clayton-Smith Julie Désir Harinder Gill Marie T Greally Erkan Koparir Merel C van Maarle Sara MacKay Geert Mortier Jenny Morton David Sillence Catheline Vilain Ian Young Klaus Zerres Martine Le Merrer Arnold Munnich Carine Le Goff Antonio Rossi Valérie Cormier-Daire
Affiliations

Affiliation

  • 1 Departement de Génétique, INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades, Paris, France.
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.

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