Novel mutations in MEN1, CDKN1B and AIP genes in patients with multiple endocrine neoplasia type 1 syndrome in Spain

Clin Endocrinol (Oxf). 2012 May;76(5):719-24. doi: 10.1111/j.1365-2265.2011.04269.x.

Abstract

Context: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder mostly owing to a genetic defect in MEN1 gene. Not all patients with MEN1 phenotype present a defect in this gene. Thus, other genes like CDKN and AIP have been showed to be involved in MEN1-like patients.

Objective: The aim of this study was to perform a genetic screening in our cohort or patients with suspected MEN1 syndrome by direct sequencing analysis of MEN1, CDKN1B and AIP, and dosage analysis of MEN1 and AIP.

Results: A total of 79 different sporadic and familial cases with the MEN1 phenotype have been studied, in which 34 of them (48%) present a mutation in MEN1 gene. In two patients without a detectable mutation in MEN1 gene, we have identified a novel missense mutation (c.163G>A/p.Ala55Thr) in CDKN1B gene and a novel frameshift mutation (c.825_845delCGCGGCCGTGTGGAATGCCCA/p. His275GlnfsX49) in AIP gene, respectively.

Conclusions: Our data support that MEN1 gene is the main target for genetic analysis in clinical MEN1 syndrome. We confirm that in those patients without MEN1 gene mutation, other genes such as CDKN1B/p27Kip, or AIP in those including pituitary tumours should also be tested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • DNA Mutational Analysis
  • Frameshift Mutation
  • Genetic Testing
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Multiple Endocrine Neoplasia Type 1 / diagnosis
  • Multiple Endocrine Neoplasia Type 1 / genetics*
  • Mutation*
  • Mutation, Missense
  • Proto-Oncogene Proteins / genetics*
  • Spain
  • Syndrome

Substances

  • CDKN1B protein, human
  • Intracellular Signaling Peptides and Proteins
  • MEN1 protein, human
  • Proto-Oncogene Proteins
  • aryl hydrocarbon receptor-interacting protein
  • Cyclin-Dependent Kinase Inhibitor p27