Abstract
Familial isolated pituitary adenomas (FIPA) constitute 2–3% of pituitary tumours. AIP is the most commonly mutated gene in FIPA. We herein report a novel germline mutation of the AIP gene in a family with FIPA. We present two patients, a father and his 12-year-old daughter, diagnosed clinically and using laboratory measures with acromegaly-gigantism. Both underwent transsphenoidal hypophyseal surgery for macroadenomas. We initially detected a novel heterozygous germline AIP mutation, c.836G>A (p.W279*), in the father’s DNA. We then found the same mutation in his affected daughter. Pituitary adenomas associated with AIP mutations mostly present as FIPA (68%) at an early age (78% occur at <30 years old). They are often growth hormone (GH) — or prolactin — secreting macroadenomas (88%) that have already extended beyond the sella at the time of diagnosis. Acromegalic cases are resistant to somatostatin analogues and multimodal management is frequently essential to control the disease. Our patients had normalized GH/IGF-1 values soon after surgery, although enough time may not have elapsed to reach final cure. While penetrance of the disease can be as low as 10% in FIPA, especially children and young patients with somatotropinoma and prolactinoma should be surveyed for inactivating mutations or deletions in AIP. Determining the causative mutations may be of assistance in early diagnosis, treatment success, and genetic counseling.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P, 2015 Genetic mutations in sporadic pituitary adenomas—what to screen for? Nat Rev Endocrinol 11: 43–54.
Daly AF, Tichomirowa MA, Beckers A, 2009 The epidemiology and genetics of pituitary adenomas. Best Pract Res Clin Endocrinol Metab 23: 543–554.
Verloes A, Stevenaert A, Teh BT, Petrossians P, Beckers A, 1999 Familial acromegaly: case report and review of the literature. Pituitary 1: 273–277.
Daly AF, Jaffrain-Rea ML, Ciccarelli A, et al, 2006 Clinical characterization of familial isolated pituitary adenomas. J Clin Endocrinol Metab 91: 3316–3323.
Vierimaa O, Georgitsi M, Lehtonen R, et al, 2006 Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 312: 1228–1230.
Daly AF, Vanbellinghen JF, Khoo SK, et al, 2007 Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab 92: 1891–1896.
Chahal HS, Chappie JP, Frohman LA, Grossman AB, Korbonits M, 2010 Clinical, genetic and molecular characterization of patients with familial isolated pituitary adenomas (FIPA). Trends Endocrinol Metab 21: 419–427.
Linnert M, Haupt K, Lin YJ, et al, 2012 NMR assignments of the FKBP-type PPIase domain of the human aryl-hydrocarbon receptor-interacting protein (AIP). Biomol NMR Assign 6: 209–212.
Ozfirat Z, Korbonits M, 2010 AIP gene and familial isolated pituitary adenomas. Mol Cell Endocrinol 326: 71–79.
Morgan RM, Hernandez-Ramirez LC, Trivellin G, et al, 2012 Structure of the TPR domain of AIP: lack of client protein interaction with the C-terminal alpha-7 helix of the TPR domain of AIP is sufficient for pituitary adenoma predisposition. PLoS One 7: e53339.
Daly AF, Beckers A, 2015 Familial isolated pituitary adenomas (FIPA) and mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocrinol Metab Clin North Am 44: 19–25.
Stiles CE, Korbonits M 2000 Familial Isolated Pituitary Adenoma. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, et al, editors. Endotext. South Dartmouth (MA).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cansu, G.B., Taşkıran, B., Trivellin, G. et al. A novel truncating AIP mutation, p.W279*, in a familial isolated pituitary adenoma (FIPA) kindred. Hormones 15, 441–444 (2016). https://doi.org/10.14310/horm.2002.1692
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.14310/horm.2002.1692