63/168 (37.5%) had coding region mutations in the known CdLS genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), with 75% of the causal variants affecting the coding region of NIPBL. Given the almost universal association of severe typical CdLS with NIPBL, we estimated that ~20% of the unexplained cases are likely to be due to cryptic mutations or mosaicism at this locus. This evidence concerns the gene SMC1A and Cornelia de Lange syndrome.