Early onset acromegaly associated with a novel deletion in CDKN1B 5'UTR region

Endocrine. 2015 May;49(1):58-64. doi: 10.1007/s12020-015-0540-y. Epub 2015 Feb 4.

Abstract

Genetic alterations frequently are involved in the development of a pituitary adenoma in young age. We here characterize the functional role of a deletion in CDKN1B 5'-UTR region (c.-29_-26delAGAG) identified in an acromegalic patient that developed a growth hormone in pituitary adenoma during childhood. Our results show that the identified novel heterozygous deletion in the CDKN1B 5'-UTR region associates with a reduction in CDKN1B mRNA levels, a predicted altered secondary mRNA structure, and a reduced CDKN1B 5'-UTR transcriptional activity in vitro. The patient displayed loss of heterozygosity in the same CDKN1B 5'-UTR region at tissue level and the 5'UTR region containing the deleted sequence encompasses a GRE. These findings indicate that the identification of functional alterations of newly discovered genetic derangements need to be fully characterized and always correlated with the clinical manifestations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Acromegaly / genetics*
  • Adult
  • Age of Onset
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • Female
  • Gene Deletion
  • Humans

Substances

  • 5' Untranslated Regions
  • CDKN1B protein, human
  • Cyclin-Dependent Kinase Inhibitor p27