Although the cause of familial isolated pituitary adenoma (FIPA) remains unknown 
in many cases, germline 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 germline 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 germline 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.