Phenotypic discordance upon paternal or maternal transmission of duplications of the 11p15 imprinted regions

Eur J Med Genet. Nov-Dec 2009;52(6):404-8. doi: 10.1016/j.ejmg.2009.08.006. Epub 2009 Sep 6.

Abstract

We report on two families in which the parental origin of duplications of the BWS imprinted regions on chromosome 11p15 influences the phenotype. In family A the transmission of a t(4; 11)(q35; p15.5) translocation results in duplication of BWSIC1 and BWSIC2. If this duplication is transmitted from the father, the extra chromosomal material has the paternal imprint. This results in overexpression of IGF2 and consequently an overgrowth phenotype. If the duplication is transmitted from the mother, the extra chromosomal material has the maternal imprint, resulting in overexpression of CDKN1C and a growth retardation phenotype. In family B an interstitial duplication of BWSIC1 results in an overgrowth phenotype when inherited from the father, similar to family A. However, no change in phenotype is observed if the duplication is transmitted through the mother suggesting that increased dosage of maternally expressed genes in the duplicated region has limited effect on the phenotype.

MeSH terms

  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 11*
  • Chromosomes, Human, Pair 4 / genetics
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics
  • Female
  • Genomic Imprinting*
  • Humans
  • Phenotype
  • Pregnancy

Substances

  • CDKN1C protein, human
  • Cyclin-Dependent Kinase Inhibitor p57