The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas

Mutational hot-spot or founder effect?

G. Occhi, M. L. Jaffrain-Rea, G. Trivellin, N. Albiger, F. Ceccato, E. De Menis, M. Angelini, S. Ferasin, A. Beckers, F. Mantero, C. Scaroni

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: Mutations in the aryl hydrocarbon receptor interacting protein [AIP) gene have been described in about 15% of kindreds with familial isolated pituitary adenomas and in a minority of early onset sporadic pituitary adenomas (PA). Among the AIP mutations reported so far, the R304X (A/PR304X) represents, together with the "Finnish mutation" Q14X, the most common one. Methods: Three AIPR304X Italian families, including a newly reported kindred, have been genotyped for 12 genetic markers surrounding the AIP gene in order to look for a potential founder effect in Italy. Disease penetrance and genotype-phenotype correlations were also addressed. Results: Analysis of chromosome 11′ genetic markers revealed a common haplotype in 2 AIPR304X kindreds originating from central Italy. Overall, 17 mutations carriers were identified, including 7 patients and 10 unaffected subjects, respectively, arguing in this case for a disease penetrance of 41%. Mean age at diagnosis was 19.1±6.7 yr old, with females tending to be older than males. Though most PA were somatotropinomas (6/7), a great variability in disease severity was observed, even between subjects sharing the same at-risk haplotype. Conclusion: These data provide strong evidence for a new founder effect of the AIPR304X mutation in central Italy and the observed variations in disease severity point out the role of additional genetic or environmental factors in such kindreds.

Original languageEnglish
Pages (from-to)800-805
Number of pages6
JournalJournal of Endocrinological Investigation
Volume33
Issue number11
DOIs
Publication statusPublished - Dec 2010

Fingerprint

Founder Effect
Mutation
Italy
Penetrance
Genes
Pituitary Neoplasms
Genetic Markers
Haplotypes
Chromosomes, Human, Pair 11
Gene Order
Genetic Association Studies
aryl hydrocarbon receptor-interacting protein
Familial Isolated Pituitary Adenoma

Keywords

  • AIP
  • FIPA
  • Founder effect
  • Haplotype analysis
  • Pituitary adenoma

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas : Mutational hot-spot or founder effect? / Occhi, G.; Jaffrain-Rea, M. L.; Trivellin, G.; Albiger, N.; Ceccato, F.; De Menis, E.; Angelini, M.; Ferasin, S.; Beckers, A.; Mantero, F.; Scaroni, C.

In: Journal of Endocrinological Investigation, Vol. 33, No. 11, 12.2010, p. 800-805.

Research output: Contribution to journalArticle

Occhi, G, Jaffrain-Rea, ML, Trivellin, G, Albiger, N, Ceccato, F, De Menis, E, Angelini, M, Ferasin, S, Beckers, A, Mantero, F & Scaroni, C 2010, 'The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas: Mutational hot-spot or founder effect?', Journal of Endocrinological Investigation, vol. 33, no. 11, pp. 800-805. https://doi.org/10.3275/6956
Occhi, G. ; Jaffrain-Rea, M. L. ; Trivellin, G. ; Albiger, N. ; Ceccato, F. ; De Menis, E. ; Angelini, M. ; Ferasin, S. ; Beckers, A. ; Mantero, F. ; Scaroni, C. / The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas : Mutational hot-spot or founder effect?. In: Journal of Endocrinological Investigation. 2010 ; Vol. 33, No. 11. pp. 800-805.
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AU - Jaffrain-Rea, M. L.

AU - Trivellin, G.

AU - Albiger, N.

AU - Ceccato, F.

AU - De Menis, E.

AU - Angelini, M.

AU - Ferasin, S.

AU - Beckers, A.

AU - Mantero, F.

AU - Scaroni, C.

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N2 - Background: Mutations in the aryl hydrocarbon receptor interacting protein [AIP) gene have been described in about 15% of kindreds with familial isolated pituitary adenomas and in a minority of early onset sporadic pituitary adenomas (PA). Among the AIP mutations reported so far, the R304X (A/PR304X) represents, together with the "Finnish mutation" Q14X, the most common one. Methods: Three AIPR304X Italian families, including a newly reported kindred, have been genotyped for 12 genetic markers surrounding the AIP gene in order to look for a potential founder effect in Italy. Disease penetrance and genotype-phenotype correlations were also addressed. Results: Analysis of chromosome 11′ genetic markers revealed a common haplotype in 2 AIPR304X kindreds originating from central Italy. Overall, 17 mutations carriers were identified, including 7 patients and 10 unaffected subjects, respectively, arguing in this case for a disease penetrance of 41%. Mean age at diagnosis was 19.1±6.7 yr old, with females tending to be older than males. Though most PA were somatotropinomas (6/7), a great variability in disease severity was observed, even between subjects sharing the same at-risk haplotype. Conclusion: These data provide strong evidence for a new founder effect of the AIPR304X mutation in central Italy and the observed variations in disease severity point out the role of additional genetic or environmental factors in such kindreds.

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