ID 109644
Author
Iwata, Takeo Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School KAKEN Search Researchers
Yamada, Shozo Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital
Ito, Junko Department of Pediatrics, Toranomon Hospital
Inoshita, Naoko Department of Pathology, Toranomon Hospital
Mizusawa, Noriko Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Ono, Shinji Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
Yoshimoto, Katsuhiko Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
familial isolated pituitary adenoma
acromegaly
aryl hydrocarbon receptor-interacting protein
loss of heterozygosity
Content Type
Journal Article
Description
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.
Journal Title
Endocrine Pathology
ISSN
10463976
NCID
AA10803175
Volume
25
Issue
3
Start Page
273
End Page
281
Sort Key
273
Published Date
2014-09
Remark
© 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.
EDB ID
Published Source
Endocrine Pathology (2014) Volume 25 Issue 3 p.273–281
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Oral Sciences