HUMAN MUTATION, cilt.33, ss.1261-1266, 2012 (SCI İndekslerine Giren Dergi)
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 beta-D-xyloside, suggesting that CANT1 plays a role in proteoglycan metabolism. Hum Mutat 33:1261-1266, 2012. (c) 2012 Wiley Periodicals, Inc.