Abstract | BACKGROUND: METHODS: Germline DNA samples of 131 Italian sporadic acromegalic patients including 38 individuals with multiple tumors, and of six FIPA families (four homogeneous for prolactinomas and two heterogeneous with prolactin/nonfunctioning pituitary adenomas) were collected in a multicentric collaborative study. The prevalence of AIP and CDKN1B gene point mutations and copy number variations were evaluated. RESULTS: Two novel (IVS3+1G>A and c.871G>A) and one previously described (c.911G>A) AIP mutations were detected in four apparently sporadic cases (3.1%) with relatively high age at diagnosis (49+/-18, range 30-67). No mutations/rearrangements were detected in FIPA families. The highly conserved c.871G>A substitution was detected in a patient who also carried a MEN1 mutation suggesting that she is a double heterozygote. The possible pathogenic effect on AIP splicing of the silent substitution c.144G>A found in another patient was ruled out using a minigene-based approach. CDKN1B mutations/rearrangements were neither identified in patients with multiple neoplasia nor in FIPA families. CONCLUSION: AIP is mutated in about 3% of apparently sporadic acromegalic patients. The relatively high age at diagnosis, as well as its sporadic presentation, suggests that these patients are carriers of mutations with reduced pathogenicity. p27(KIP1) is unlikely to represent the common unifying nonendocrine etiology for acromegaly and cancer.
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Authors | G Occhi, G Trivellin, F Ceccato, P De Lazzari, G Giorgi, S Demattè, F Grimaldi, R Castello, M V Davì, G Arnaldi, L Salviati, G Opocher, F Mantero, C Scaroni |
Journal | European journal of endocrinology
(Eur J Endocrinol)
Vol. 163
Issue 3
Pg. 369-76
(Sep 2010)
ISSN: 1479-683X [Electronic] England |
PMID | 20530095
(Publication Type: Comparative Study, Journal Article, Multicenter Study)
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Chemical References |
- CDKN1B protein, human
- Intracellular Signaling Peptides and Proteins
- aryl hydrocarbon receptor-interacting protein
- Cyclin-Dependent Kinase Inhibitor p27
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Topics |
- Acromegaly
(complications, epidemiology, genetics)
- Adolescent
- Adult
- Aged
- Amino Acid Sequence
- Cyclin-Dependent Kinase Inhibitor p27
- Female
- Germ-Line Mutation
(genetics)
- Humans
- Intracellular Signaling Peptides and Proteins
(genetics)
- Italy
(epidemiology)
- Male
- Middle Aged
- Molecular Sequence Data
- Multiple Endocrine Neoplasia
(complications, epidemiology, genetics)
- Pedigree
- Prevalence
- Young Adult
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