HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Naves, L. A Articles by Beckers, A. Search for Related Content PubMed PubMed Citation Articles by Naves, L. A Articles by Beckers, A.

Variable pathological and clinical features of a large Brazilian family harboring a mutation in the aryl hydrocarbon receptor-interacting protein gene

¹ Department of Endocrinology, Internal Medicine, University of Brasília, Brasília DF, Brazil, ² Departments of Endocrinology and ³ Molecular Genetics, Centre Hospitalier Universitaire de Liège, University of Liège, 4000 Liège, Belgium, ⁴ Department of Experimental Medicine, University of L’Aquila, 67100 L’Aquila and Neuromed, Istituto di Ricovero e Cura a Carattere Scientifico, 86077 Pozzili, Italy, ⁵ Department of Pathology, University of Brasília, Brasília DF, Brazil and ⁶ Laboratory Sabin, Brasília DF, Brazil

(Correspondence should be addressed to L A Naves; Email: lunaves{at}unb.br)

Background: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations occur in 15% of familial isolated pituitary adenoma (FIPA) cases. To date, studies have focused on the identification of such mutations in large international cohorts. Detailed genetic and clinical studies within AIP mutation-positive families have been limited.

Aim: To undertake a comprehensive study of a large Brazilian FIPA kindred with an E174 frameshift (E174fs) AIP mutation to assess clinical, hormonal, and radiological features in mutation carriers.

Methods: The kindred included 122 subjects across six generations; all underwent clinical examination. Genetic studies were performed to identify E174fs mutation carriers. E174fs-positive subjects underwent magnetic resonance imaging (MRI) and hormonal assessments.

Results: Of the ten germline AIP mutation carriers, three had pituitary tumors, while seven were asymptomatic carriers. Three patients with pituitary tumors showed variability in terms of tumor phenotype (two with acromegaly, one with prolactinoma, or mixed prolactin/GH-secreting tumor) and age at diagnosis; both patients with acromegaly had poor responses to octreotide. Tumor AIP immunohistochemistry from the operated patient showed decreased expression when compared with normal tissue. Two adult subjects with normal MRI had elevated IGF-I in the absence of other causes. A 2-year-old child with the E174fs mutation and a normal MRI had premature thelarche, ovarian development, and advanced bone age in the absence of other underlying causes.

Conclusions: The penetrance of pituitary tumors in AIP mutation-positive adult subjects was 33.3%, while clinical/hormonal features were variable. The features noted in AIP-mutation carriers in this kindred suggest that clinical characteristics of such carriers may extend beyond pituitary tumors.

This article has been cited by other articles:

				C. A. Leontiou, M. Gueorguiev, J. van der Spuy, R. Quinton, F. Lolli, S. Hassan, H. S. Chahal, S. C. Igreja, S. Jordan, J. Rowe, et al. The Role of the Aryl Hydrocarbon Receptor-Interacting Protein Gene in Familial and Sporadic Pituitary Adenomas J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2390 - 2401. [Abstract] [Full Text] [PDF]

				A. Beckers and A. F Daly The clinical, pathological, and genetic features of familial isolated pituitary adenomas Eur. J. Endocrinol., October 1, 2007; 157(4): 371 - 382. [Abstract] [Full Text] [PDF]