In man, the mild forms of CdLS that have been linked to mutations in cohesin subunit genes (Smc1 and Smc3 [61],[62]) appear to be caused by specific, rare missense mutations (i.e., very likely not simple loss-of-function alleles), also consistent with the idea that the cause of CdLS is not simply a reduced level of cohesin function, but rather the selective disruption of specific functions in which Nipbl and cohesin work together. This evidence concerns the gene NIPBL and Cornelia de Lange syndrome.