Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma

Rodrigo A. Toledo, Delmar M. Lourenço, Bernardo Liberman, Malebranche B C Cunha-Neto, Maria G. Cavalcanti, Cinthia B. Moyses, Sergio P A Toledo, Patricia L Dahia

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Context: Acromegaly is usually sporadic, but familial cases occur in association with several familial pituitary tumor syndromes. Recently mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were associated with familial pituitary adenoma predisposition. Objective: The objective of the study was to investigate the status of AIP in a pituitary tumor predisposition family. Settings: The study was conducted at a nonprofit academic center and medical centers. Patients: Eighteen members of a Brazilian family with acromegaly were studied. Results: A novel germline mutation in the AIP gene, Y268X, predicted to generate a protein lacking two conserved domains, was identified in four members of this family: two siblings with early-onset acromegaly; a third, 41-yr-old sibling with a microadenoma but no clinical features of disease, and his 3-yr-old son. No changes were found in 14 unaffected at-risk relatives or 92 healthy controls. Conclusions: We confirm the role of the AIP gene in familial acromegaly. This finding increases the spectrum of molecular defects that can give rise to pituitary adenoma susceptibility. Establishment of genotype-phenotype correlations in AIP mutant tumors will determine whether AIP screening can be used as a tool for clinical surveillance and genetic counseling of families with pituitary tumor predisposition. The underlying basis for the phenotypic variation within AIP-mutant families and the mechanism of AIP-mediated tumorigenesis remain to be defined.

Original languageEnglish (US)
Pages (from-to)1934-1937
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number5
DOIs
StatePublished - May 2007

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Germ-Line Mutation
Pituitary Neoplasms
Acromegaly
Tumors
Genes
Siblings
Genetic Counseling
Genetic Association Studies
Screening
Nuclear Family
Carcinogenesis
Defects
aryl hydrocarbon receptor-interacting protein
Mutation
Proteins
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma. / Toledo, Rodrigo A.; Lourenço, Delmar M.; Liberman, Bernardo; Cunha-Neto, Malebranche B C; Cavalcanti, Maria G.; Moyses, Cinthia B.; Toledo, Sergio P A; Dahia, Patricia L.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 5, 05.2007, p. 1934-1937.

Research output: Contribution to journalArticle

Toledo, RA, Lourenço, DM, Liberman, B, Cunha-Neto, MBC, Cavalcanti, MG, Moyses, CB, Toledo, SPA & Dahia, PL 2007, 'Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma', Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 5, pp. 1934-1937. https://doi.org/10.1210/jc.2006-2394
Toledo, Rodrigo A. ; Lourenço, Delmar M. ; Liberman, Bernardo ; Cunha-Neto, Malebranche B C ; Cavalcanti, Maria G. ; Moyses, Cinthia B. ; Toledo, Sergio P A ; Dahia, Patricia L. / Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 5. pp. 1934-1937.
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abstract = "Context: Acromegaly is usually sporadic, but familial cases occur in association with several familial pituitary tumor syndromes. Recently mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were associated with familial pituitary adenoma predisposition. Objective: The objective of the study was to investigate the status of AIP in a pituitary tumor predisposition family. Settings: The study was conducted at a nonprofit academic center and medical centers. Patients: Eighteen members of a Brazilian family with acromegaly were studied. Results: A novel germline mutation in the AIP gene, Y268X, predicted to generate a protein lacking two conserved domains, was identified in four members of this family: two siblings with early-onset acromegaly; a third, 41-yr-old sibling with a microadenoma but no clinical features of disease, and his 3-yr-old son. No changes were found in 14 unaffected at-risk relatives or 92 healthy controls. Conclusions: We confirm the role of the AIP gene in familial acromegaly. This finding increases the spectrum of molecular defects that can give rise to pituitary adenoma susceptibility. Establishment of genotype-phenotype correlations in AIP mutant tumors will determine whether AIP screening can be used as a tool for clinical surveillance and genetic counseling of families with pituitary tumor predisposition. The underlying basis for the phenotypic variation within AIP-mutant families and the mechanism of AIP-mediated tumorigenesis remain to be defined.",
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