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

Mathilde Nizon, 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 MortierJenny Morton, David Sillence, Catheline Vilain, Ian Young, Klaus Zerres, Martine Le Merrer, Arnold Munnich, Carine Le Goff, Antonio Rossi, Valérie Cormier-Daire

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1261-1266
Number of pages6
JournalHuman Mutation
Issue number8
Publication statusPublished - Aug 2012


  • CANT1
  • CHST3
  • Desbuquois dysplasia type 1 and type 2
  • Proteoglycan metabolism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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