PMID- 17185897
OWN - NLM
STAT- MEDLINE
DCOM- 20070116
LR  - 20191026
IS  - 1720-8386 (Electronic)
IS  - 0391-4097 (Linking)
VI  - 29
IP  - 10
DP  - 2006 Nov
TI  - New splicing mutation of MEN1 gene affecting the translocation of menin to the 
      nucleus.
PG  - 888-93
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a syndrome inherited in an 
      autosomal dominant trait caused by the inactivation of the tumor suppressor gene 
      MEN1. OBJECTIVE: To communicate a family with a new heterozygous germ line 
      mutation in the intronic region of MEN1 gene and to study its influence in the 
      menin expression. PATIENTS AND METHODS: We studied 5 members of a family with 
      symptomatic hyperparathyroidism (HPT). One of them had also a neuroendocrine 
      pancreatic tumor, and 2 had non-functional multinodular cortical adrenal 
      hyperplasia compatible with the diagnosis of MEN1. After the mutation was 
      identified, HSP92II restriction enzyme was used to determine both zygosity and 
      segregation of the mutation. RT-PCR from leukocyte's isolated mRNA and western 
      blot from pancreatic tumor tissue were performed. In vitro studies were done in 
      Chinese hamster ovary (CHO) cells transfected with reporter minigenes carrying 
      the coding regions spanning exon (EX)-intron 9 and EX10 with the mutant and the 
      wild type sequences. RESULTS: We identified a heterozygous G-to-T substitution in 
      the intron-EX junction (IVS9-1 G>T) of MEN1 gene in the index case and the family 
      members. The mRNA from patient's leukocytes was larger (934 bp) in comparison to 
      the normal transcript (717 bp). Immunoblot analysis demonstrated that wild type 
      (67 kDa) and two additional mutant proteins (approximately 55 and approximately 
      90 kDa) were expressed in the pancreatic tissue. The in vitro study showed a 45% 
      nuclear localization of the mutated menin signal and a 95% in the wild type 
      protein. CONCLUSIONS: We identified a new intronic heterozygous germ line 
      mutation (IVS9-1G>T) of MEN1 gene in a family affected by MEN1 syndrome. This 
      mutation alters the splice acceptor site of intron 9 that promotes an incorrect 
      splicing, generating aberrant proteins without the nuclear localization signals 
      necessary for the normal menin translocation to the nucleus.
FAU - Tala, H P
AU  - Tala HP
AD  - Department of Endocrinology, School of Medicine, Pontificia Universidad Catolica 
      de Chile, Santiago, Chile.
FAU - Carvajal, C A
AU  - Carvajal CA
FAU - Gonzalez, A A
AU  - Gonzalez AA
FAU - Garrido, J L
AU  - Garrido JL
FAU - Tobar, J
AU  - Tobar J
FAU - Solar, A
AU  - Solar A
FAU - Campino, C
AU  - Campino C
FAU - Arteaga, E
AU  - Arteaga E
FAU - Fardella, C E
AU  - Fardella CE
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Aged, 80 and over
MH  - Alternative Splicing
MH  - Cell Nucleus/*metabolism
MH  - Child
MH  - Chile
MH  - DNA/genetics
MH  - Female
MH  - Germ-Line Mutation/*genetics
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Nucleic Acid Amplification Techniques
MH  - Pedigree
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Sequence Analysis, DNA
EDAT- 2006/12/23 09:00
MHDA- 2007/01/17 09:00
CRDT- 2006/12/23 09:00
PHST- 2006/12/23 09:00 [pubmed]
PHST- 2007/01/17 09:00 [medline]
PHST- 2006/12/23 09:00 [entrez]
AID - 3254 [pii]
AID - 10.1007/BF03349192 [doi]
PST - ppublish
SO  - J Endocrinol Invest. 2006 Nov;29(10):888-93. doi: 10.1007/BF03349192.