A novel C-terminal nonsense mutation, Q315X, of the aryl hydrocarbon receptor-interacting protein gene in a Japanese familial isolated pituitary adenoma family

Although the cause of familial isolated pituitary adenoma (FIPA) remains unknown in many cases, germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene were identified in approximately 20% of families with FIPA. We investigated the AIP gene mutation by a standard sequencing method in 12 members of a Japanese two-generation FIPA family, which includes 3 patients with early-onset acromegaly. Multiplex ligation-dependent probe amplification analysis in a tumor sample was attempted to examine the loss of heterozygosity (LOH) in the locus. The effect of the detected mutation on cell proliferation was investigated. A germ-line mutation of c.943C>T (p.Q315X) generating an AIP protein with the C-terminal end deleted was found in the FIPA family. Biallelic inactivation of AIP by a combination of the germ-line mutation and LOH at 11q13 was confirmed in the tumor. The nonsense mutation disrupted the ability to inhibit cell proliferation. We conclude that p.Q315X mutation in the AIP gene is a pathogenic variant and the C-terminal region of AIP plays an important role in the predisposition to pituitary adenomas.

© Springer Science+Business Media New York 2014
The final publication is available at Springer via http://dx.doi.org/10.1007/s12022-014-9318-7.