Endocrine Abstracts

Germline AIP gene mutations have been linked with familial isolated pituitary adenomas (FIPA). Inactivating mutations of AIP have also been reported in seemingly sporadic pituitary adenomas, particularly of early onset, aggressive, and GH secreting.

Aim: To assess the frequency and type of germline AIP gene mutations in patients with apparently sporadic PMAs.

Material: The study included 31 consecutive patients with pituitary macroadenoma (17 males, 14 females; median age at diagnosis 43 years), followed in the Outpatient Clinic of the Endocricology Department, University Hospital in Krakow. 13 subjects have been diagnosed with non-functioning pituitary adenoma (NFPA), ten – acromegaly, four – prolactinoma, two – Cushing’s disease, one – TSH-oma, and one with gonadotropinoma. Median tumor size at diagnosis was 30 mm.

Methods: DNA of all participants was isolated from whole peripheral blood. The six exons of the AIP gene were sequenced using sanger sequencing (ABI 3500). Sequences were compared to reference data at NCBI, accordingly: NM_003977.2 and NP_003968.2. Nucleotide conservativity was estimated by PhyoP. The mutation influence on protein was estimated by PROVEAN protein.

Results: Two patients (9.8%) have been suggested to harbor a germline missense mutation in exon 3 of the AIP gene c.[377A>T];[=], p.[Q126L]; [=] (patient 1 – a 53 year old female with suprasellar NFPA, harboring also SNP rs2276020/c.516>t/p.Asp= in exon 4–5; patient 2 – a 41 year old female with 17 mm ACTH-secreting macroadenoma). The mutation, to our knowledge so far unreported, is localized in a highly conservative region of the gene and most probably leads to abnormal function of AIP suppressor gene.

Conclusions: As both mutation carriers would not be selected for AIP gene sequencing based on clinical features, it seems feasible to search for germline AIP gene mutations in every patient with PMA. The presented report is an initial one, the recruitment of patients is still pending.