2. Academic Validation
  3. Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study

Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study

  • Endocrine. 2016 Dec;54(3):762-767. doi: 10.1007/s12020-016-0862-4.
Francesco Ferraù 1,  P D Romeo 2,  S Puglisi 2,  M Ragonese 2,  M L Torre 2,  C Scaroni 3,  G Occhi 4,  E De Menis 5,  G Arnaldi 6,  F Trimarchi 2,  S Cannavò 2
Affiliations

Affiliations

  • 1 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. [email protected].
  • 2 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.
  • 3 Endocrinology Unit, Department of Medicine, Padova University Hospital, Padua, Italy.
  • 4 Department of Biology, University of Padova, Padua, Italy.
  • 5 Department of Internal Medicine, General Hospital of Montebelluna, Treviso, Italy.
  • 6 Department of Endocrinology and Metabolic Diseases, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
PMID: 26815903 DOI: 10.1007/s12020-016-0862-4
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.

Keywords

AIP; Acromegaly; FIPA; GPR101; Somatotropinoma.

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