Somatic mosaicism in Cornelia de Lange syndrome: a further contributor to the wide clinical expressivity?

摘要: Cornelia de Lange syndrome (CdLS) is a rare, congenital characterized by growth retardation, dysmorphic face, mental retardation and limb reduction defects. Clinical manifestations of CdLS can be extremely variable. Mutations in NIPBL, SMC1A SMC3 genes, encoding for regulator two subunits the cohesin complex, respectively, are found 60-65% patients. We report on male with who mosaic c.2827delA mutation NIPBL gene. Allele quantitation pyrosequencing showed presence about 10% 33% DNA samples from peripheral blood buccal smears, respectively. The patient shows complex phenotype: psychomotor characteristic severe forms CdLS, while absence defects major malformations typical mild phenotype. He also has depigmentation areas following Blashko lines, an unusual finding which been associated mosaicism other genetic conditions. This case represents first evidence somatic explains phenotype as compared to that predicted truncating mutation. Besides confirming clinical heterogeneity this raises likely underestimated rate known genes points complexity addressing genotype-phenotype correlations.