Mutation of CANT1 causes Desbuquois dysplasia

Desbuquois dysplasia is an autosomal recessive dysplasia characterized by severe growth restriction and distinct hand and proximal femur appearance in addition to cognitive impairment. The critical interval for this disease has been mapped to 17q25.3 using homozygosity mapping. We have identified a newborn with classical features of the disease whose parents are first cousins. Assuming genetic homogeneity of this disorder, we were able to narrow the critical interval to a region that only contained 10 annotated genes by combining the results of our homozygosity mapping with those of Others. Serial Sequencing of the genes contained within the interval revealed a 5 bp duplication in Calcium-Activated Nucleotidase 1 gene (CANT1), consistent with the very recent report by Huber et al. [Huber et al. (2009); Am J Hum Genet 85:706-710]. This report cements the role of CANT1 in the causation of this dysplasia and demonstrates the high value of even single cases in the setting of genetically homogeneous disorders when homozygosity mapping is used.