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dc.contributor.authorRadian, S
dc.contributor.authorDiekmann, Y
dc.contributor.authorGabrovska, P
dc.contributor.authorHolland, B
dc.contributor.authorBradley, L
dc.contributor.authorWallace, H
dc.contributor.authorStals, K
dc.contributor.authorBussell, A-M
dc.contributor.authorMcGurren, K
dc.contributor.authorCuesta, M
dc.contributor.authorRyan, AW
dc.contributor.authorHerincs, M
dc.contributor.authorHernandez-Ramirez, LC
dc.contributor.authorHolland, A
dc.contributor.authorSamuels, J
dc.contributor.authorAflorei, ED
dc.contributor.authorBarry, S
dc.contributor.authorDenes, J
dc.contributor.authorPernicova, I
dc.contributor.authorStiles, CE
dc.contributor.authorTrivellin, G
dc.contributor.authorMcCloskey, R
dc.contributor.authorAjzensztejn, M
dc.contributor.authorAbid, N
dc.contributor.authorAkker, SA
dc.contributor.authorMercado, M
dc.contributor.authorCohen, M
dc.contributor.authorThakker, RV
dc.contributor.authorBaldeweg, S
dc.contributor.authorBarkan, A
dc.contributor.authorMusat, M
dc.contributor.authorLevy, M
dc.contributor.authorOrme, SM
dc.contributor.authorUnterlaender, M
dc.contributor.authorBurger, J
dc.contributor.authorKumar, AV
dc.contributor.authorEllard, S
dc.contributor.authorMcPartlin, J
dc.contributor.authorMcManus, R
dc.contributor.authorLinden, GJ
dc.contributor.authorAtkinson, B
dc.contributor.authorBalding, DJ
dc.contributor.authorAgha, A
dc.contributor.authorThompson, CJ
dc.contributor.authorHunter, SJ
dc.contributor.authorThomas, MG
dc.contributor.authorMorrison, PJ
dc.contributor.authorKorbonits, M
dc.date.accessioned2021-02-05T01:31:15Z
dc.date.available2021-02-05T01:31:15Z
dc.date.issued2017-01-01
dc.identifier.citationRadian, S., Diekmann, Y., Gabrovska, P., Holland, B., Bradley, L., Wallace, H., Stals, K., Bussell, A. -M., McGurren, K., Cuesta, M., Ryan, A. W., Herincs, M., Hernandez-Ramirez, L. C., Holland, A., Samuels, J., Aflorei, E. D., Barry, S., Denes, J., Pernicova, I. ,... Korbonits, M. (2017). Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland. HUMAN MUTATION, 38 (1), pp.78-85. https://doi.org/10.1002/humu.23121.
dc.identifier.issn1059-7794
dc.identifier.urihttp://hdl.handle.net/11343/260428
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, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI 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%) versus 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 (1,275-5,000) years. tMRCA-based simulations predicted 432 (90-5,175) current carriers, including 86 affected (18-1,035) 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.
dc.languageEnglish
dc.publisherWILEY-BLACKWELL
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleIncreased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland
dc.typeJournal Article
dc.identifier.doi10.1002/humu.23121
melbourne.affiliation.departmentSchool of Mathematics and Statistics
melbourne.affiliation.facultyScience
melbourne.source.titleHuman Mutation
melbourne.source.volume38
melbourne.source.issue1
melbourne.source.pages78-85
dc.rights.licenseCC BY
melbourne.elementsid1103964
melbourne.contributor.authorBalding, David
dc.identifier.eissn1098-1004
melbourne.accessrightsOpen Access


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