CDKN1B

Deficiency of the Cyclin-Dependent Kinase Inhibitor, CDKN1B, Results in Overgrowth and Neurodevelopmental Delay.

"Germline mutations in the cyclin-dependent kinase inhibitor, CDKN1B, have been described in patients with multiple endocrine neoplasia (MEN), a cancer predisposition syndrome with adult onset neoplasia and no additional phenotypes. Here, we describe the first human case of CDKN1B deficiency, which recapitulates features of the murine CDKN1B knockout mouse model, including gigantism and neurodevelopmental defects. Decreased mRNA and protein expression of CDKN1B were confirmed in the proband's peripheral blood, which is not seen in MEN syndrome patients. We ascribed the decreased protein level to a maternally derived deletion on chromosome 12p13 encompassing the CDKN1B locus (which reduced mRNA expression) and a de novo allelic variant (c.-73G>A) in the CDKN1B promoter (which reduced protein translation)."

"The p27-/- mouse exhibits gigantism and hyperplasia of multiple organs including
the brain"

"the effect of p27 absence and gigantism [is due] to increased Sox2 levels, as p27 directly inhibits Sox2 expression"

"In p27-/- mice, the gigantism was due to Sox2-dependent increase in thickness of the pituitary progenitor layer."

"Germline heterozygote mutations in human CDKN1C are related to Beckwith-Wiedemann Syndrome, which is associated with overgrowth, developmental delay and tumour predisposition"