Pure proximal deletion of chromosome 21 and kyphosis

We report on two unrelated patients with a proximal deletion of the long arm of chromosome 21. The deletion encompassed 14.5 Mb of DNA. Molecular studies showed that the two telomeric breakpoints were within the same DNA clone (BAC RP11-56D12). The centromeric breakpoints, however, were separated by only 250 kb of DNA (BAC RP11-645E14 and RP11-324B9). The phenotype observed in the two patients was very different, as patient 2, who had the largest deletion, had severe kyphosis not observed in patient 1. Previous studies have identified a 6 Mb region of chromosome 21 associated with severe kyphosis. Interestingly, this region overlaps the 250 kb segment deleted in patient 2. We suggest that one gene (NT011512.4) located in this small overlapping region might be responsible for severe kyphosis.