Identification of **CANT1** mutations in Desbuquois dysplasia

Huber, Céline; Oulès, Bénédicte; Bertoli, Marta; Mortier, Geert; et al.

doi:10.1016/J.AJHG.2009.10.001

Title

Identification of **CANT1** mutations in Desbuquois dysplasia

Author

Huber, Céline

Oulès, Bénédicte

Bertoli, Marta

Mortier, Geert

et al.

Abstract

Desbuquois dysplasia is a severe condition characterized by short stature, joint laxity, scoliosis, and advanced carpal ossification with a delta phalanx. Studying nine Desbuquois families, we identified seven distinct mutations in the Calcium-Activated Nucleotidase 1 gene (CANT1), which encodes a soluble UDP-preferring nucleotidase belonging to the apyrase family. Among the seven mutations, four were nonsense mutations (Del 5′ UTR and exon 1, p.P245RfsX3, p.S303AfsX20, and p.W125X), and three were missense mutations (p.R300C, p.R300H, and p.P299L) responsible for the change of conserved amino acids located in the seventh nucleotidase conserved region (NRC). The arginine substitution at position 300 was identified in five out of nine families. The specific function of CANT1 is as yet unknown, but its substrates are involved in several major signaling functions, including Ca2+ release, through activation of pyrimidinergic signaling. Importantly, using RT-PCR analysis, we observed a specific expression in chondrocytes. We also found electron-dense material within distended rough endoplasmic reticulum in the fibroblasts of Desbuquois patients. Our findings demonstrate the specific involvement of a nucleotidase in the endochondral ossification process.

Language

French

Source (journal)

The American journal of human genetics / American Society of Human Genetics [Bethesda, Md] - New York, N.Y., 1949, currens

Publication

New York, N.Y. : 2009

ISSN

0002-9297 [print]

1537-6605 [online]

DOI

10.1016/J.AJHG.2009.10.001

Volume/pages