AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience.

2.50
Hdl Handle:
http://hdl.handle.net/11287/605114
Title:
AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience.
Authors:
Ramírez-Rentería, C.; Hernández-Ramírez, L. C.; Portocarrero-Ortiz, L.; Vargas, G.; Melgar, V.; Espinosa, E.; Espinosa-de-Los-Monteros, A. L.; Sosa, E.; González, B.; Zúñiga, S.; Unterländer, M.; Burger, J.; Stals, K.; Bussell, A-M.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Dang, M.; Iacovazzo, D.; Kapur, S.; Gabrovska, P.; Radian, S.; Roncaroli, F.; Korbonits, M.; Mercado, M.
Abstract:
Although aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare in sporadic acromegaly, their prevalence among young patients is nonnegligible. The objectives of this study were to evaluate the frequency of AIP mutations in a cohort of Mexican patients with acromegaly with disease onset before the age of 30 and to search for molecular abnormalities in the AIP gene in teeth obtained from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly (51 females) with disease onset <30 years was analysed (median age of disease onset of 23 years) and correlated with clinical, biochemical and imaging characteristics. Sequencing was also carried out in DNA extracted from teeth of the Tampico Giant. Five patients (7 %) harboured heterozygous, germline mutations of the AIP gene. In two of them (a 9-year-old girl with gigantism and a young man with symptoms of GH excess since age 14) the c.910C>T (p.Arg304Ter), well-known truncating mutation was identified; in one of these two cases and her identical twin sister, the mutation proved to be a de novo event, since neither of their parents were found to be carriers. In the remaining three patients, new mutations were identified: a frameshift mutation (c.976_977insC, p.Gly326AfsTer), an in-frame deletion (c.872_877del, p.Val291_Leu292del) and a nonsense mutation (c.868A > T, p.Lys290Ter), which are predicted to be pathogenic based on in silico analysis. Patients with AIP mutations tended to have an earlier onset of acromegaly and harboured larger and more invasive tumours. A previously described genetic variant of unknown significance (c.869C > T, p.Ala299Val) was identified in DNA from the Tampico Giant. The prevalence of AIP mutations in young Mexican patients with acromegaly is similar to that of European cohorts. Our results support the need for genetic evaluation of patients with early onset acromegaly.
Citation:
AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience. 2016 Aug;53(2):402-11 Endocrine
Publisher:
Springer
Journal:
Endocrine
Issue Date:
31-Mar-2016
URI:
http://hdl.handle.net/11287/605114
DOI:
10.1007/s12020-016-0930-9
PubMed ID:
27033541
Additional Links:
http://dx.doi.org/10.1007/s12020-016-0930-9
Type:
Journal Article
Language:
en
ISSN:
1559-0100
Appears in Collections:
Molecular Genetics; Molecular Genetics; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorRamírez-Rentería, C.en
dc.contributor.authorHernández-Ramírez, L. C.en
dc.contributor.authorPortocarrero-Ortiz, L.en
dc.contributor.authorVargas, G.en
dc.contributor.authorMelgar, V.en
dc.contributor.authorEspinosa, E.en
dc.contributor.authorEspinosa-de-Los-Monteros, A. L.en
dc.contributor.authorSosa, E.en
dc.contributor.authorGonzález, B.en
dc.contributor.authorZúñiga, S.en
dc.contributor.authorUnterländer, M.en
dc.contributor.authorBurger, J.en
dc.contributor.authorStals, K.en
dc.contributor.authorBussell, A-M.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorDang, M.en
dc.contributor.authorIacovazzo, D.en
dc.contributor.authorKapur, S.en
dc.contributor.authorGabrovska, P.en
dc.contributor.authorRadian, S.en
dc.contributor.authorRoncaroli, F.en
dc.contributor.authorKorbonits, M.en
dc.contributor.authorMercado, M.en
dc.date.accessioned2016-04-12T15:54:46Zen
dc.date.available2016-04-12T15:54:46Zen
dc.date.issued2016-03-31en
dc.identifier.citationAIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience. 2016 Aug;53(2):402-11 Endocrineen
dc.identifier.issn1559-0100en
dc.identifier.pmid27033541en
dc.identifier.doi10.1007/s12020-016-0930-9en
dc.identifier.urihttp://hdl.handle.net/11287/605114en
dc.description.abstractAlthough aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare in sporadic acromegaly, their prevalence among young patients is nonnegligible. The objectives of this study were to evaluate the frequency of AIP mutations in a cohort of Mexican patients with acromegaly with disease onset before the age of 30 and to search for molecular abnormalities in the AIP gene in teeth obtained from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly (51 females) with disease onset <30 years was analysed (median age of disease onset of 23 years) and correlated with clinical, biochemical and imaging characteristics. Sequencing was also carried out in DNA extracted from teeth of the Tampico Giant. Five patients (7 %) harboured heterozygous, germline mutations of the AIP gene. In two of them (a 9-year-old girl with gigantism and a young man with symptoms of GH excess since age 14) the c.910C>T (p.Arg304Ter), well-known truncating mutation was identified; in one of these two cases and her identical twin sister, the mutation proved to be a de novo event, since neither of their parents were found to be carriers. In the remaining three patients, new mutations were identified: a frameshift mutation (c.976_977insC, p.Gly326AfsTer), an in-frame deletion (c.872_877del, p.Val291_Leu292del) and a nonsense mutation (c.868A > T, p.Lys290Ter), which are predicted to be pathogenic based on in silico analysis. Patients with AIP mutations tended to have an earlier onset of acromegaly and harboured larger and more invasive tumours. A previously described genetic variant of unknown significance (c.869C > T, p.Ala299Val) was identified in DNA from the Tampico Giant. The prevalence of AIP mutations in young Mexican patients with acromegaly is similar to that of European cohorts. Our results support the need for genetic evaluation of patients with early onset acromegaly.en
dc.languageENGen
dc.language.isoenen
dc.publisherSpringeren
dc.relation.urlhttp://dx.doi.org/10.1007/s12020-016-0930-9en
dc.rightsArchived with thanks to Endocrine.en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleAIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience.en
dc.typeJournal Articleen
dc.identifier.journalEndocrineen
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.