title: A novel germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene in an Italian family with gigantism.
abstract: OBJECTIVE
  Acromegaly usually occurs as a sporadic disease, but it may be a part of familial pituitary tumor syndromes in rare cases. Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been associated with a predisposition to familial isolated pituitary adenoma. The aim of the present study was to evaluate the AIP gene in a patient with gigantism and in her relatives.
  
  
  METHODS
  Direct sequencing of AIP gene was performed in fourteen members of the family, spanning among three generations.
  
  
  RESULTS
  The index case was an 18-year-old woman with gigantism due to an invasive GH-secreting pituitary adenoma and a concomitant tall-cell variant of papillary thyroid carcinoma. A novel germline mutation in the AIP gene (c.685C>T, p.Q229X) was identified in the proband and in two members of her family, who did not present clinical features of acromegaly or other pituitary disorders. Eleven subjects had no mutation in the AIP gene. Two members of the family with clinical features of acromegaly refused either the genetic or the biochemical evaluation. The Q229X mutation was predicted to generate a truncated AIP protein, lacking the last two tetratricopeptide repeat domains and the final C-terminal α-7 helix.
  
  
  CONCLUSIONS
  We identified a new AIP germline mutation predicted to produce a truncated AIP protein, lacking its biological properties due to the disruption of the C-terminus binding sites for both the chaperones and the client proteins of AIP.
authors.affiliation: Section of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy, urbani@sssup.it.
authors.forename: C
authors.initials: C
authors.lastname: Urbani
authors.forename: D
authors.initials: D
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Raggi
authors.forename: M
authors.initials: M
authors.lastname: Lombardi
authors.forename: C
authors.initials: C
authors.lastname: Sardella
authors.forename: I
authors.initials: I
authors.lastname: Scattina
authors.forename: I
authors.initials: I
authors.lastname: Lupi
authors.forename: L
authors.initials: L
authors.lastname: Manetti
authors.forename: L
authors.initials: L
authors.lastname: Tomisti
authors.forename: C
authors.initials: C
authors.lastname: Marcocci
authors.forename: E
authors.initials: E
authors.lastname: Martino
authors.forename: F
authors.initials: F
authors.lastname: Bogazzi
mesh_terms: D000293:Adolescent; D002277:Carcinoma / Q000150:complications / Q000235:genetics*; D002291:Carcinoma, Papillary; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D005877:Gigantism / Q000209:etiology / Q000235:genetics*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007558:Italy; D010375:Pedigree; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000150:complications / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein