PMID- 17766710
OWN - NLM
STAT- MEDLINE
DCOM- 20071119
LR  - 20220408
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 157
IP  - 3
DP  - 2007 Sep
TI  - Multiple endocrine neoplasia type 1 in Northern Finland; clinical features and 
      genotype phenotype correlation.
PG  - 285-94
AB  - OBJECTIVE: The existence of genotype-phenotype correlation in multiple endocrine 
      neoplasia type 1 (MEN1) is controversial. Two founder mutations of the MEN1 gene 
      in Northern Finland gave us an opportunity to compare clinical features among 
      heterozygotes of different mutations. DESIGN AND METHODS: Study cohort included 
      82 MEN1 heterozygotes who were tested for MEN1 during the years 1982-2001. 
      Medical records were reviewed for manifestations of MEN1, other tumours and cause 
      of death by the end of August 2003. Logistic regression analysis was used in 
      evaluating the impact of age, gender and mutational status of affected 
      heterozygotes on the likelihood of developing manifestations of MEN1. RESULTS: 
      Founder mutations 1466del12 and 1657insC were found in 39 and 29 individuals, and 
      D418N, G156R and R527X mutations in 9, 3 and 2 individuals respectively. Except 
      for pituitary adenoma and nonfunctional pancreatic tumour (NFPT), age was a risk 
      factor for all the disease manifestations. For NFPT, frameshift/nonsense 
      mutations (1657insC, R527X) gave an odds ratio (OR) of 3.26 (95% confidence 
      intervals (CI), 1.27-8.33; P = 0.014) compared with in-frame/missense mutations 
      (1466del12, D418N, G156R); including the founder mutation carriers (n = 68) only, 
      the 1657insC mutation gave an OR of 3.56 (CI, 1.29-9.83; P = 0.015). For 
      gastrinoma, in-frame/missense mutations predicted the risk with an OR of 6.77 
      (CI, 1.31-35.0; P = 0.022), and in the founder mutations group the 1466del12 
      mutation gave an OR of 15.09 (CI, 1.73-131.9, P = 0.014). CONCLUSIONS: In this 
      study population, NFPT was more common in the frameshift/nonsense or 1657insC 
      mutation carriers, whereas gastrinoma was more common in the in-frame/missense or 
      1466del12 mutation carriers.
FAU - Vierimaa, O
AU  - Vierimaa O
AD  - Department of Clinical Genetics, Oulu University Hospital, PB 24, FIN-90029, Oys, 
      Oulu, Finland. outi.vierimaa@oulu.fi
FAU - Ebeling, T M L
AU  - Ebeling TM
FAU - Kytola, S
AU  - Kytola S
FAU - Bloigu, R
AU  - Bloigu R
FAU - Eloranta, E
AU  - Eloranta E
FAU - Salmi, J
AU  - Salmi J
FAU - Korpi-Hyovalti, E
AU  - Korpi-Hyovalti E
FAU - Niskanen, L
AU  - Niskanen L
FAU - Orvola, A
AU  - Orvola A
FAU - Elovaara, E
AU  - Elovaara E
FAU - Gynther, A
AU  - Gynther A
FAU - Sane, T
AU  - Sane T
FAU - Valimaki, M
AU  - Valimaki M
FAU - Ignatius, J
AU  - Ignatius J
FAU - Leisti, J
AU  - Leisti J
FAU - Salmela, P I
AU  - Salmela PI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Codon, Nonsense)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adolescent
MH  - Adrenal Gland Neoplasms/genetics/mortality
MH  - Adult
MH  - Aged
MH  - Carcinoma, Neuroendocrine/genetics/mortality
MH  - Child
MH  - Codon, Nonsense
MH  - Female
MH  - Finland/epidemiology
MH  - Founder Effect
MH  - Frameshift Mutation
MH  - Gastrointestinal Neoplasms/genetics/mortality
MH  - Genotype
MH  - Humans
MH  - Hyperparathyroidism, Primary/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/*mortality
MH  - Mutation, Missense
MH  - Pancreatic Neoplasms/genetics/mortality
MH  - Phenotype
MH  - Pituitary Neoplasms/genetics/mortality
MH  - Proto-Oncogene Proteins/*genetics
MH  - Risk Factors
EDAT- 2007/09/04 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/09/04 09:00
PHST- 2007/09/04 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/09/04 09:00 [entrez]
AID - 157/3/285 [pii]
AID - 10.1530/EJE-07-0195 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2007 Sep;157(3):285-94. doi: 10.1530/EJE-07-0195.