Mis3 variants, perhaps suggesting that these variants have less severe consequences. Indeed, cdLS severity is highly correlated to the expression levels of NIPBL (Kaur et al., 2016), and the de novo Mis3 variants that we observed were in exons 29 and 47 whereas exon 10 has the greatest proportion of pathogenic CdLS variants (Mannini et al., 2013). In addition, both patients have some phenotypic aspects that are consistent with CdLS: (1) the TIC Genetics proband has failure to thrive in childhood with adult short stature (final height in the fifth percentile for males), generalized anxiety, and irritable bowel, and (2) the TSAICG proband has developmental delay, intellectual disability, and mild hearing loss, although birthweight, height, and weight were within normal limits.
