Increased Population Risk of AIP-related Acromegaly and Gigantism in Ireland.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620031
Title:
Increased Population Risk of AIP-related Acromegaly and Gigantism in Ireland.
Authors:
Radian, S.; Diekmann, Y.; Gabrovska, P.; Holland, B.; Bradley, L.; Wallace, H.; Stals, Karen; Bussell, Anna-Marie; McGurren, K.; Cuesta, M.; Ryan, A. W.; Herincs, M.; Hernández-Ramírez, L. C.; Holland, A.; Samuels, J.; Aflorei, E. D.; Barry, S.; Dénes, J.; Pernicova, I.; Stiles, C. E.; Trivellin, G.; McCloskey, R.; Azjensztejn, M.; Abid, N.; Akker, S. A.; Mercado, M.; Cohen, M.; Thakker, R. V.; Baldeweg, S.; Barkan, A.; Musat, M.; Levy, M. L.; Orme, S.; Unterländer, M.; Burger, J.; Kumar, A. V.; Ellard, Sian ( 0000-0002-7620-5526 ) ; McPartlin, J.; McManus, R.; Linden, G. J.; Atkinson, B.; Balding, D.; Agha, A.; Thompson, C. J.; Hunter, S. J.; Thomas, M. G.; Morrison, P. J.; Korbonits, M.
Abstract:
The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304*; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1000 Greater Belfast (both in NI) and 2094 Republic of Ireland (ROI) volunteers and in 116 acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) vs. non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1275-5000) years. tMRCA-based simulations predicted 432 (90-5175) current carriers, including 86 affected (18-1035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically-targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease. This article is protected by copyright. All rights reserved.
Citation:
Increased Population Risk of AIP-related Acromegaly and Gigantism in Ireland. 2017 Jan;38(1):78-85. Epub 2016 Oct 4: Hum. Mutat.
Publisher:
Wiley
Journal:
Human mutation
Issue Date:
21-Sep-2016
URI:
http://hdl.handle.net/11287/620031
DOI:
10.1002/humu.23121
PubMed ID:
27650164
Additional Links:
http://dx.doi.org/10.1002/humu.23121
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1098-1004
Appears in Collections:
Molecular Genetics; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorRadian, S.en
dc.contributor.authorDiekmann, Y.en
dc.contributor.authorGabrovska, P.en
dc.contributor.authorHolland, B.en
dc.contributor.authorBradley, L.en
dc.contributor.authorWallace, H.en
dc.contributor.authorStals, Karenen
dc.contributor.authorBussell, Anna-Marieen
dc.contributor.authorMcGurren, K.en
dc.contributor.authorCuesta, M.en
dc.contributor.authorRyan, A. W.en
dc.contributor.authorHerincs, M.en
dc.contributor.authorHernández-Ramírez, L. C.en
dc.contributor.authorHolland, A.en
dc.contributor.authorSamuels, J.en
dc.contributor.authorAflorei, E. D.en
dc.contributor.authorBarry, S.en
dc.contributor.authorDénes, J.en
dc.contributor.authorPernicova, I.en
dc.contributor.authorStiles, C. E.en
dc.contributor.authorTrivellin, G.en
dc.contributor.authorMcCloskey, R.en
dc.contributor.authorAzjensztejn, M.en
dc.contributor.authorAbid, N.en
dc.contributor.authorAkker, S. A.en
dc.contributor.authorMercado, M.en
dc.contributor.authorCohen, M.en
dc.contributor.authorThakker, R. V.en
dc.contributor.authorBaldeweg, S.en
dc.contributor.authorBarkan, A.en
dc.contributor.authorMusat, M.en
dc.contributor.authorLevy, M. L.en
dc.contributor.authorOrme, S.en
dc.contributor.authorUnterländer, M.en
dc.contributor.authorBurger, J.en
dc.contributor.authorKumar, A. V.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorMcPartlin, J.en
dc.contributor.authorMcManus, R.en
dc.contributor.authorLinden, G. J.en
dc.contributor.authorAtkinson, B.en
dc.contributor.authorBalding, D.en
dc.contributor.authorAgha, A.en
dc.contributor.authorThompson, C. J.en
dc.contributor.authorHunter, S. J.en
dc.contributor.authorThomas, M. G.en
dc.contributor.authorMorrison, P. J.en
dc.contributor.authorKorbonits, M.en
dc.date.accessioned2016-09-29T14:15:04Z-
dc.date.available2016-09-29T14:15:04Z-
dc.date.issued2016-09-21-
dc.identifier.citationIncreased Population Risk of AIP-related Acromegaly and Gigantism in Ireland. 2017 Jan;38(1):78-85. Epub 2016 Oct 4: Hum. Mutat.en
dc.identifier.issn1098-1004-
dc.identifier.pmid27650164-
dc.identifier.doi10.1002/humu.23121-
dc.identifier.urihttp://hdl.handle.net/11287/620031-
dc.description.abstractThe aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304*; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1000 Greater Belfast (both in NI) and 2094 Republic of Ireland (ROI) volunteers and in 116 acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) vs. non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1275-5000) years. tMRCA-based simulations predicted 432 (90-5175) current carriers, including 86 affected (18-1035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically-targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease. This article is protected by copyright. All rights reserved.en
dc.languageENG-
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://dx.doi.org/10.1002/humu.23121en
dc.rightsArchived with thanks to Human mutationen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleIncreased Population Risk of AIP-related Acromegaly and Gigantism in Ireland.en
dc.typeJournal Articleen
dc.identifier.journalHuman mutationen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionIn press (epub ahead of print)en

Related articles on PubMed

All Items in RD&E Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.