AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience
- PDF / 1,072,565 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 39 Downloads / 151 Views
ENDOCRINE GENETICS/EPIGENETICS
AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience Claudia Ramı´rez-Renterı´a1,2 • Laura C. Herna´ndez-Ramı´rez4 • Lesly Portocarrero-Ortiz3 • Guadalupe Vargas1 • Virgilio Melgar2 • Etual Espinosa1,2 • Ana Laura Espinosa-de-los-Monteros1 • Ernesto Sosa1 • Baldomero Gonza´lez1,2 • Sergio Zu´n˜iga1 • Martina Unterla¨nder5 • Joachim Burger5 • Karen Stals6 • Anne-Marie Bussell6 • Sian Ellard6 • Mary Dang4 • Donato Iacovazzo4 • Sonal Kapur4 • Plamena Gabrovska4 • Serban Radian4 • Federico Roncaroli7 • Ma´rta Korbonits4 • Moise´s Mercado1,2 Received: 28 January 2016 / Accepted: 16 March 2016 Ó Springer Science+Business Media New York 2016
1
Experimental Endocrinology Unit/Endocrine Service, Hospital de Especialidades Centro Me´dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Sur 132 number 142, Suite 210, Colonia las Americas, Mexico City 01120, Mexico
2
Neurological Center, Centro Me´dico ABC, Mexico City, Mexico
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.
3
Endocrinology Service, Instituto Nacional de Neurologı´a y Neurocirugı´a, Mexico City, Mexico
Keywords
4
Centre for Endocrinology, The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, UK
Introduction
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’’. P
Data Loading...
