CANT1 protein is encoded by a gene that belongs to the apyrase family. It comprises 401 amino acids long with a molecular mass of 45 kDa. It localizes in the endoplasmic reticulum membrane and within the Golgi apparatus. This enzyme functions as a calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. It has a very low activity towards ADP and even lower activity towards ATP, but it does not hydrolyze AMP and GMP. This enzyme is also involved in proteoglycan synthesis. Defects in this enzyme are the cause of are Desbuquois dysplasia, a rare condition of an autosomal recessive inheritance, characterized by antenatal and postnatal growth restriction, distinct hand and proximal femur appearance, advanced carpal ossification in addition to cognitive impairment. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies.
The CANT1 gene is localized on chromosome 17q25.3. It spans 18 kb long and consists of five coding exons. Researchers have identified mutations in this gene in patients affected with Desbuquois dysplasia with hand anomalies. These include deletions, insertions, duplications, missense, nonsense and intronic splice site mutations.
Using direct sequencing for CANT1 gene, Huber et al. (2009) identified an insertion of GCGCC nucleotides in exon four (907-911) in Desbuquois dysplasia patient, resulting in a p.S303AfsX20 amino acid change. At the age of 3-months, the boy died due to cardio-respiratory failure. His parents were consanguineous of Moroccan origin.
Faden et al. (2010) described a newborn male with Desbuquois dysplasia. The patient was born to consanguineous parents of Saudi origin. The patient suffered from severe growth retardation, abnormally short limbs, clubfeet, facial dysmorphia and bilateral congenital glaucoma. X-rays revealed severe Desbuquois features of the hand as well as characteristic ‘monkey-wrench’ appearance of the proximal femur. The patient succumbed to severe respiratory distress at one month of age. Homozygosity mapping revealed a region of homozygosity on chromosome 17q. By combining the data with a previously reported linkage interval, the region was narrowed to 1.2 Mb and carried 10 genes. Mutation analysis then revealed a novel 5 bp duplication (c.893-894insGCCGC) in the CANT1 gene. This was predicted to result in a frameshift and premature truncation of the protein at codon 325. Both parents were found to be carriers of the mutation.
Huber et al. (2009) screened the CANT1 gene in an Emirati male with Desbuquois dysplasia disorder and born to consanguineous parents. The missense c.899G>A mutation was identified. The mutation is expected to result in a p.R300H substitution. This mutation is located in the NCR7-encoding region, a highly conserved region.