PMID- 22129891
OWN - NLM
STAT- MEDLINE
DCOM- 20120420
LR  - 20161018
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 166
IP  - 3
DP  - 2012 Mar
TI  - Functional characterization of a rare germline mutation in the gene encoding the 
      cyclin-dependent kinase inhibitor p27Kip1 (CDKN1B) in a Spanish patient with 
      multiple endocrine neoplasia-like phenotype.
PG  - 551-60
LID - 10.1530/EJE-11-0929 [doi]
AB  - OBJECTIVE: The aim of this study was to investigate the presence of germline 
      mutations in the CDKN1B gene that encodes the cyclin-dependent kinase (Cdk) 
      inhibitor p27 in multiple endocrine neoplasia 1 (MEN1)-like Spanish index 
      patients. The CDKN1B gene has recently been identified as a tumor susceptibility 
      gene for MEN4, with six germline mutations reported so far in patients with a 
      MEN-like phenotype but negative for MEN1 mutations. DESIGN AND METHODS: Fifteen 
      Spanish index cases with MEN-like symptoms were screened for mutations in the 
      CDKN1B gene and the mutant variant was studied functionally by 
      transcription/translation assays in vitro and in transiently transfected HeLa 
      cells. RESULTS: We report the identification of a heterozygous GAGA deletion in 
      the 5'-UTR of CDKN1B, NM_004064.3:c.-32_-29del, in a patient affected by gastric 
      carcinoid tumor and hyperparathyroidism. This deletion falls inside the region 
      that is responsible for CDKN1B transcription and is predicted to destroy a 
      secondary stem and loop structure that includes the GAGAGA element responsible 
      for ribosome recruitment. Accordingly, in vitro studies of coupled 
      transcription/translation assays and transient transfection in HeLa cells showed 
      that the GAGA deletion in the CDKN1B 5'-UTR significantly impairs the 
      transcription of downstream reporter luciferase (of  approximately 40-60%) and, possibly, the 
      translation of the corresponding mRNA. This mutation was associated with a 
      significant reduction in the amount of CDKN1B mRNA in peripheral blood leukocytes 
      from the patient, as demonstrated by quantitative real-time PCR. CONCLUSIONS: Our 
      results confirm that germline CDKN1B mutations may predispose to a human MEN4 
      condition and add novel evidence that alteration in the transcription/translation 
      rate of CDKN1B mRNA might be the mechanism implicated in tumor susceptibility.
FAU - Malanga, Donatella
AU  - Malanga D
AD  - Dipartimento di Medicina Sperimentale e Clinica G Salvatore, Universita Magna 
      Graecia, Campus Universitario Germaneto, 88100 Catanzaro, Italy.
FAU - De Gisi, Silvia
AU  - De Gisi S
FAU - Riccardi, Miriam
AU  - Riccardi M
FAU - Scrima, Marianna
AU  - Scrima M
FAU - De Marco, Carmela
AU  - De Marco C
FAU - Robledo, Mercedes
AU  - Robledo M
FAU - Viglietto, Giuseppe
AU  - Viglietto G
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111130
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (CDKN1B protein, human)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Base Sequence
MH  - Cyclin-Dependent Kinase Inhibitor p27/*genetics
MH  - Female
MH  - Germ-Line Mutation/*genetics
MH  - HeLa Cells
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Multiple Endocrine Neoplasia Type 1/diagnosis/*genetics
MH  - *Phenotype
MH  - Spain
EDAT- 2011/12/02 06:00
MHDA- 2012/04/21 06:00
CRDT- 2011/12/02 06:00
PHST- 2011/12/02 06:00 [entrez]
PHST- 2011/12/02 06:00 [pubmed]
PHST- 2012/04/21 06:00 [medline]
AID - EJE-11-0929 [pii]
AID - 10.1530/EJE-11-0929 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2012 Mar;166(3):551-60. doi: 10.1530/EJE-11-0929. Epub 2011 Nov 
      30.