Article: article from journal or magazin.
Identification of CANT1 mutations in Desbuquois dysplasia.
American Journal of Human Genetics
Publication types: Case Reports ; Journal Article
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.
5' Untranslated Regions, Adolescent, Adult, Amino Acid Sequence, Amino Acid Substitution, Arginine/metabolism, Bone Diseases, Developmental/genetics, Bone Diseases, Developmental/radiography, Calcium/metabolism, Cells, Cultured, Child, Preschool, Chondrocytes/metabolism, Chromosomes, Human, Pair 17, Codon, Nonsense, Consanguinity, Endoplasmic Reticulum, Rough/ultrastructure, Exons, Fatal Outcome, Female, Fibroblasts/ultrastructure, Homozygote, Humans, Infant, Infant, Newborn, Male, Molecular Sequence Data, Mutation, Mutation, Missense, Nuclear Family, Nucleotidases/genetics, RNA, Messenger/metabolism
Last modification date