PMID- 21678021
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20211203
IS  - 1559-0100 (Electronic)
IS  - 1355-008X (Linking)
VI  - 40
IP  - 3
DP  - 2011 Dec
TI  - Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian 
      family.
PG  - 481-5
LID - 10.1007/s12020-011-9501-2 [doi]
AB  - To describe the coexistence of mutations of both the multiple endocrine neoplasia 
      type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and evaluate if 
      it could be associated with more aggressive clinical manifestations of the two 
      syndromes. Blood samples were obtained for genetic and biochemical analyses. The 
      RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding regions, 
      including the exon-intron boundaries, were amplified by PCR and directly 
      sequenced. We identified two germline mutations in the proband: the first one, 
      K666M, located at the exon 11 of RET proto-oncogene and the second one, 
      IVS4+1G>T, located in the MEN1 gene. The functional characterization of IVS4+1G>T 
      variation, located in the splicing donor site of exon 4 of MEN1 gene, caused the 
      in-frame junction of exon 3 to exon 5, thus obtaining a shorter protein. The same 
      proband's germline mutations were found in 16 relatives out of 21 screened 
      subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both the mutations. This is the 
      second report in literature of coexistence in the same family of germline 
      mutations of both RET proto-oncogene and MEN1 gene. The simultaneous presence of 
      the two mutations was not apparently associated with more aggressive diseases, 
      since at last follow-up all patients appeared to be disease-free or well 
      compensated by medical therapy; finally, no one exhibited metastatic diseases.
FAU - Mastroianno, Sandra
AU  - Mastroianno S
AD  - Unit of Cardiology, Scientific Institute Casa Sollievo della Sofferenza, 71013, 
      San Giovanni Rotondo, Italy.
FAU - Torlontano, Massimo
AU  - Torlontano M
FAU - Scillitani, Alfredo
AU  - Scillitani A
FAU - D'Aloiso, Leonardo
AU  - D'Aloiso L
FAU - Verrienti, Antonella
AU  - Verrienti A
FAU - Bonfitto, Nazario
AU  - Bonfitto N
FAU - De Bonis, Antonio
AU  - De Bonis A
FAU - D'Agruma, Leonardo
AU  - D'Agruma L
FAU - Muscarella, Lucia Anna
AU  - Muscarella LA
FAU - Guarnieri, Vito
AU  - Guarnieri V
FAU - Dicembrino, Franca
AU  - Dicembrino F
FAU - Maranghi, Marianna
AU  - Maranghi M
FAU - Durante, Cosimo
AU  - Durante C
FAU - Filetti, Sebastiano
AU  - Filetti S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110617
PL  - United States
TA  - Endocrine
JT  - Endocrine
JID - 9434444
RN  - 0 (MAS1 protein, human)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Family
MH  - Female
MH  - *Germ-Line Mutation
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/complications/*genetics
MH  - Multiple Endocrine Neoplasia Type 2a/complications/*genetics
MH  - Pedigree
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-ret/*genetics
MH  - Severity of Illness Index
MH  - Young Adult
EDAT- 2011/06/17 06:00
MHDA- 2012/03/27 06:00
CRDT- 2011/06/17 06:00
PHST- 2011/05/15 00:00 [received]
PHST- 2011/06/03 00:00 [accepted]
PHST- 2011/06/17 06:00 [entrez]
PHST- 2011/06/17 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
AID - 10.1007/s12020-011-9501-2 [doi]
PST - ppublish
SO  - Endocrine. 2011 Dec;40(3):481-5. doi: 10.1007/s12020-011-9501-2. Epub 2011 Jun 
      17.