title: Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study.
abstract: This multicentric study aimed to investigate the prevalence of the G protein-coupled receptor 101 (GPR101) p.E308D variant and aryl hydrocarbon receptor interacting protein (AIP) gene mutations in a representative cohort of Italian patients with acromegaly. 215 patients with GH-secreting pituitary adenomas, referred to 4 Italian referral centres for pituitary diseases, have been included. Three cases of gigantism were present. Five cases were classified as FIPA. All the patients have been screened for germline AIP gene mutations and GPR101 gene p.E308D variant. Heterozygous AIP gene variants have been found in 7 patients (3.2 %). Five patients carried an AIP mutation (2.3 %; 4 females): 3 patients harboured the p.R3O4Q mutation, one had the p.R304* mutation and the last one the IVS3+1G>A mutation. The prevalence of AIP mutations was 3.3 % and 2.8 % when considering only the patients diagnosed when they were <30 or <40-year old, respectively. Furthermore, 2.0 % of the patients with a pituitary macroadenoma and 4.2 % of patients resistant to somatostatin analogues treatment were found to harbour an AIP gene mutation. None of the patients was found to carry the GPR101 p.E308D variant. The prevalence of AIP gene mutations among our sporadic and familial acromegaly cases was similar to that one reported in previous studies, but lower when considering only the cases diagnosed before 40 years of age. The GPR101 p.E308D change is unlikely to have a role in somatotroph adenomas tumorigenesis, since none of our sporadic or familial patients tested positive for this variant.
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, UOC di Endocrinologia, Pad. H, 4° piano, AOU Policlinico Gaetano Martino, Via Consolare Valeria, 1, 98125, Messina, Italy. francesco.ferrau1@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraù
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, UOC di Endocrinologia, Pad. H, 4° piano, AOU Policlinico Gaetano Martino, Via Consolare Valeria, 1, 98125, Messina, Italy.
authors.forename: P D
authors.initials: PD
authors.lastname: Romeo
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, UOC di Endocrinologia, Pad. H, 4° piano, AOU Policlinico Gaetano Martino, Via Consolare Valeria, 1, 98125, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Puglisi
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, UOC di Endocrinologia, Pad. H, 4° piano, AOU Policlinico Gaetano Martino, Via Consolare Valeria, 1, 98125, Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ragonese
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, UOC di Endocrinologia, Pad. H, 4° piano, AOU Policlinico Gaetano Martino, Via Consolare Valeria, 1, 98125, Messina, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Torre
authors.affiliation: Endocrinology Unit, Department of Medicine, Padova University Hospital, Padua, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Scaroni
authors.affiliation: Department of Biology, University of Padova, Padua, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Occhi
authors.affiliation: Department of Internal Medicine, General Hospital of Montebelluna, Treviso, Italy.
authors.forename: E
authors.initials: E
authors.lastname: De Menis
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Arnaldi
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, UOC di Endocrinologia, Pad. H, 4° piano, AOU Policlinico Gaetano Martino, Via Consolare Valeria, 1, 98125, Messina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Trimarchi
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, UOC di Endocrinologia, Pad. H, 4° piano, AOU Policlinico Gaetano Martino, Via Consolare Valeria, 1, 98125, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cannavò
mesh_terms: D000172:Acromegaly / Q000235:genetics*; D000328:Adult; D015331:Cohort Studies; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000150:complications / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C000594175:GPR101 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C103265:aryl hydrocarbon receptor-interacting protein
keywords: AIP; Acromegaly; FIPA; GPR101; Somatotropinoma
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