title: A novel truncating AIP mutation, p.W279*, in a familial isolated pituitary adenoma (FIPA) kindred.
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.
authors.affiliation: Division of Endocrinology and Metabolism, Yunus Emre State Hospital, 26190, Eskişehir, Turkey.
authors.forename: Güven Barış
authors.initials: GB
authors.lastname: Cansu
authors.affiliation: Division of Endocrinology and Metabolism, Yunus Emre State Hospital, 26190, Eskişehir, Turkey.
authors.forename: Bengür
authors.initials: B
authors.lastname: Taşkıran
authors.affiliation: Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Trivellin
authors.affiliation: Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Faucz
authors.affiliation: Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000172:Acromegaly / Q000175:diagnosis / Q000235:genetics; D000236:Adenoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005877:Gigantism / Q000175:diagnosis / Q000235:genetics; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D006579:Heterozygote; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C583557:IGF1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I