Desbuquois dysplasia

Desbuquois dysplasia (DBQD) is an autosomal recessive chondrodysplasia belonging to the multiple dislocation group; it is characterized by severe prenatal and postnatal growth retardation, joint laxity, short extremities, multiple dislocations, progressive scoliosis and facial dysmorphism. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advanced carpal and tarsal bone age. DBQD type 1 has been defined based on the presence of hand anomalies, whilst DBQD type 2 is characterised by the absence of hand anomalies. An additional DBQD phenotype, the so called Kim variant, is characterized by very short metacarpals and elongated phalanges without accessory ossification center.

In DBQD type 1 and Kim variant mutations in the CANT1 gene have been identified. The gene encodes a Calcium Activated Nucletidase 1 present in the ER/Golgi that preferentially hydrolyzes UDP followed by GDP and UTP. On the basis of its substrate preference and its localization it has been demonstrated that this enzyme play a role in proteoglycan synthesis through the hydrolysis of UDP a product of glycosyl transferase reactions. Thanks to UDP removal, glycosyltransferase reactions are not inhibited and uridin monophosphate (UMP) is exchanged with cytosolic UDP sugars through an antiporter exchanger.