Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland
Abstract Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome characterized by parathyroid, gastroenteropancreatic and pituitary neuroendocrine tumours. In Northern Finland, two founder mutations of the MEN1 gene (1466del12, 1657insC) accounting for the majority of the MEN1 cases, hav...
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ftunivoulu:oai:oulu.fi:isbn978-951-42-8822-7 2023-07-30T04:05:49+02:00 Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland Vierimaa, O. (Outi) 2008-06-17 application/pdf http://urn.fi/urn:isbn:9789514288227 eng eng University of Oulu info:eu-repo/semantics/altIdentifier/pissn/0355-3221 info:eu-repo/semantics/altIdentifier/eissn/1796-2234 info:eu-repo/semantics/openAccess © University of Oulu, 2008 genetic predisposition multiple endocrine neoplasia type 1 pituitary adenoma primary hyperparathyroidism info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion 2008 ftunivoulu 2023-07-08T20:01:22Z Abstract Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome characterized by parathyroid, gastroenteropancreatic and pituitary neuroendocrine tumours. In Northern Finland, two founder mutations of the MEN1 gene (1466del12, 1657insC) accounting for the majority of the MEN1 cases, have common ancestors born in the 18th and 19th centuries, respectively. Three small clusters of familial pituitary adenoma have also been detected, two of which could be linked by genealogy to a common ancestral couple born in the 18th century. Clinical evaluation of 82 MEN1 mutation carriers showed that age was a risk factor for most of the MEN1-related manifestations. In the whole group, nonfunctional pancreatic tumour (NFPT) was more common in the frameshift/nonsense mutation carriers (odds ratio 3.26; 95% confidence interval 1.27–8.33, P = 0.014), whereas gastrinoma was more common in the in-frame/missense mutation carriers (OR 6.77, CI 1.31–35.0, P = 0.022). In the founder mutation carriers, the 1657insC mutation predicted the risk for NFPT (OR 3.56, CI 1.29–9.83, P = 0.015), while the 1466del12 mutation was associated with the risk for gastrinoma (OR 15.1, CI 1.73–131.9, P = 0.014). The mean ages at death of the 32 obligatory MEN1 founder mutation carriers born between 1728 and 1929 were compared to those of the 29 spouses and sex-matched life expectancy estimates derived from Finnish national statistics. The ages at death of the mutation carrier males (61.1 ± 12.0 years) and females (67.2 ± 10.7 years) did not differ from the control groups. PAP (pituitary adenoma predisposition) locus was mapped in the chromosome region 11q12–11q13 by whole-genome single-nucleotide polymorphism genotyping. Combining the linkage and the gene expression array data, AIP (aryl hydrocarbon receptor interacting protein) was chosen for sequencing. The nonsense mutation Q14X was identified in the affected (acromegaly, gigantism, prolactinoma) family members and in four other patients. Loss of heterozygosity was detected in pituitary ... Doctoral or Postdoctoral Thesis Northern Finland Jultika - University of Oulu repository |
institution |
Open Polar |
collection |
Jultika - University of Oulu repository |
op_collection_id |
ftunivoulu |
language |
English |
topic |
genetic predisposition multiple endocrine neoplasia type 1 pituitary adenoma primary hyperparathyroidism |
spellingShingle |
genetic predisposition multiple endocrine neoplasia type 1 pituitary adenoma primary hyperparathyroidism Vierimaa, O. (Outi) Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland |
topic_facet |
genetic predisposition multiple endocrine neoplasia type 1 pituitary adenoma primary hyperparathyroidism |
description |
Abstract Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome characterized by parathyroid, gastroenteropancreatic and pituitary neuroendocrine tumours. In Northern Finland, two founder mutations of the MEN1 gene (1466del12, 1657insC) accounting for the majority of the MEN1 cases, have common ancestors born in the 18th and 19th centuries, respectively. Three small clusters of familial pituitary adenoma have also been detected, two of which could be linked by genealogy to a common ancestral couple born in the 18th century. Clinical evaluation of 82 MEN1 mutation carriers showed that age was a risk factor for most of the MEN1-related manifestations. In the whole group, nonfunctional pancreatic tumour (NFPT) was more common in the frameshift/nonsense mutation carriers (odds ratio 3.26; 95% confidence interval 1.27–8.33, P = 0.014), whereas gastrinoma was more common in the in-frame/missense mutation carriers (OR 6.77, CI 1.31–35.0, P = 0.022). In the founder mutation carriers, the 1657insC mutation predicted the risk for NFPT (OR 3.56, CI 1.29–9.83, P = 0.015), while the 1466del12 mutation was associated with the risk for gastrinoma (OR 15.1, CI 1.73–131.9, P = 0.014). The mean ages at death of the 32 obligatory MEN1 founder mutation carriers born between 1728 and 1929 were compared to those of the 29 spouses and sex-matched life expectancy estimates derived from Finnish national statistics. The ages at death of the mutation carrier males (61.1 ± 12.0 years) and females (67.2 ± 10.7 years) did not differ from the control groups. PAP (pituitary adenoma predisposition) locus was mapped in the chromosome region 11q12–11q13 by whole-genome single-nucleotide polymorphism genotyping. Combining the linkage and the gene expression array data, AIP (aryl hydrocarbon receptor interacting protein) was chosen for sequencing. The nonsense mutation Q14X was identified in the affected (acromegaly, gigantism, prolactinoma) family members and in four other patients. Loss of heterozygosity was detected in pituitary ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Vierimaa, O. (Outi) |
author_facet |
Vierimaa, O. (Outi) |
author_sort |
Vierimaa, O. (Outi) |
title |
Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland |
title_short |
Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland |
title_full |
Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland |
title_fullStr |
Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland |
title_full_unstemmed |
Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland |
title_sort |
multiple endocrine neoplasia type 1 (men1) and pituitary adenoma predisposition (pap) in northern finland |
publisher |
University of Oulu |
publishDate |
2008 |
url |
http://urn.fi/urn:isbn:9789514288227 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_relation |
info:eu-repo/semantics/altIdentifier/pissn/0355-3221 info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
op_rights |
info:eu-repo/semantics/openAccess © University of Oulu, 2008 |
_version_ |
1772818000486858752 |