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Should aip gene screening be recommended in family members of FIPA patients with R16H variant?

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Abstract

Germline mutations of aryl-hydrocarbon-receptor interacting protein (AIP) are associated with pituitary adenoma predisposition. They occur in 20 % of familial isolated pituitary adenoma (FIPA) and in about 3–5 % of sporadic pituitary adenomas, especially in early onset somatotropinomas and prolactinomas. Our aim was to evaluate the clinical and genetic features of a large Italian FIPA family, where an AIP variant was identified. AIP direct sequencing from genomic DNA was carried out in 16 available family members. AIP R16H carriers also underwent magnetic resonance imaging and hormonal assessments. AIP mutations were also searched in 16 patients with sporadic growth hormone-secreting pituitary adenoma and in 6 unrelated patients in whom pituitary adenoma was excluded. We found an AIP R16H variation in two family members harbouring a pituitary adenoma and in 6 unaffected family members. No AIP mutation was found neither in growth hormone-secreting pituitary adenoma patients, nor in the unrelated patients without pituitary adenoma. We report a FIPA family harbouring an AIP R16H change, supporting the hypothesis that the latter represents a variant of unknown significance.

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Acknowledgments

This work was supported by grants from the Italian Ministry of University and Research (FIRB RBAP11884 M and RBAP1153LS), Fondazione Cassa di Risparmio di Ferrara and Associazione Italiana per la Ricerca sul Cancro (AIRC) in collaboration with Laboratorio in rete del Tecnopolo “Tecnologie delle terapie avanzate” (LTTA) of the University of Ferrara. MLT was recipient of a grant of Carrozza–San Leonardo Pollicino Foundation, Messina.

Conflict of interest

There is no conflict of interest, the Authors have nothing to disclose.

Ethical standards

The authors declare that the experiments comply with the current laws of the country in which they were performed.

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Authors and Affiliations

  1. Department of Biomedical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, Ferrara, Italy

    Maria Chiara Zatelli, Rachele Rossi & Ettore degli Uberti

  2. Laboratorio in rete del Tecnopolo “Tecnologie delle terapie avanzate” (LTTA), University of Ferrara, Ferrara, Italy

    Maria Chiara Zatelli & Ettore degli Uberti

  3. Department of Clinical and Experimental Medicine and Pharmacology, Section of Endocrinology, University of Messina, Messina, Italy

    Maria Luisa Torre, Marta Ragonese, Francesco Trimarchi & Salvatore Cannavò

  4. Sezione di Endocrinologia, Pad. H, piano 4, Azienda Ospedaliera Universitaria Policlinico “G. Martino”, Via Consolare Valeria 1, 98125, Messina, Italy

    Salvatore Cannavò

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  1. Maria Chiara Zatelli
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Correspondence to Salvatore Cannavò.

Additional information

Maria Chiara Zatelli and Maria Luisa Torre have equally contributed to the study.

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Zatelli, M.C., Torre, M.L., Rossi, R. et al. Should aip gene screening be recommended in family members of FIPA patients with R16H variant?. Pituitary 16, 238–244 (2013). https://doi.org/10.1007/s11102-012-0409-5

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