Abstract | CONTEXT: OBJECTIVE: To determine the AIP mutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AIPmut carrier family members. DESIGN: This was an observational, longitudinal study conducted over 7 years. SETTING: PARTICIPANTS: FIPA families (n 216) and sporadic young-onset (30 y) pituitary adenoma patients (n 404) participated in the study. INTERVENTIONS: We performed genetic screening of patients for AIPmuts, clinical assessment of their family members, and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant. MAIN OUTCOME MEASURE(S): We assessed clinical disease in mutation carriers, comparison of characteristics of AIPmut positive and negative patients, results of GNAS1, and FGFR4 analysis. RESULTS: Thirty-seven FIPA families and 34 sporadic patients had AIPmuts. Patients with truncating AIPmuts had a younger age at disease onset and diagnosis, compared with patients with nontruncating AIPmuts. Somatic GNAS1 mutations were absent in tumors from AIPmut-positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in AIPmut-positive individuals. A total of 164 AIPmut-positive unaffected family members were identified; pituitary disease was detected in 18 of those who underwent clinical screening. CONCLUSIONS:
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Authors | Laura C Hernández-Ramírez, Plamena Gabrovska, Judit Dénes, Karen Stals, Giampaolo Trivellin, Daniel Tilley, Francesco Ferrau, Jane Evanson, Sian Ellard, Ashley B Grossman, Federico Roncaroli, Mónica R Gadelha, Márta Korbonits, International FIPA Consortium |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 100
Issue 9
Pg. E1242-54
(Sep 2015)
ISSN: 1945-7197 [Electronic] United States |
PMID | 26186299
(Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Intracellular Signaling Peptides and Proteins
- aryl hydrocarbon receptor-interacting protein
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Topics |
- Adenoma
(diagnosis, genetics, pathology)
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Child
- Child, Preschool
- Female
- Genetic Testing
- Germ-Line Mutation
- Growth Hormone-Secreting Pituitary Adenoma
(diagnosis, genetics, pathology)
- Humans
- Intracellular Signaling Peptides and Proteins
(genetics)
- Longitudinal Studies
- Male
- Middle Aged
- Mutation
- Pituitary Neoplasms
(diagnosis, genetics, pathology)
- Prospective Studies
- Young Adult
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