Screening of Gene Variations in a Cohort of Turkish Patients with Young-Onset Sporadic Hormone-Secreting Pituitary Adenomas.

Aryl hydrocarbon receptor-interacting protein () gene mutations have long been associated with apparently sporadic pituitary adenomas (PAs) with a prevalence range of 0-12%. The aim of this study was to evaluate the frequency of germline variations in a large cohort of apparently sporadic PAs diagnosed before the age of 40 years, who did not exhibit hypercalcemia and/or MEN1 syndrome components during long-term follow-up. A total of 97 patients, diagnosed with functional PAs ≤40 years old, composed of somatotropinoma ( = 55), prolactinoma ( = 25), and corticotrophinoma ( = 17), were recruited for this study. Fifty-one of these patients [somatotropinoma ( = 30), prolactinoma ( = 15), and corticotrophinoma ( = 11)] were previously reported as mutation-negative by Sanger sequencing. The entire coding sequence of the gene, along with exon/intron boundaries and the untranslated regions of 41 newly recruited patients, were sequenced for germline variations. In addition, all patients were subjected to multiplex ligation-dependent probe amplification to detect copy number variations in the gene. The c.911G>A: p.Arg304Gln (rs104894190) variant was detected in only two patients with functional PA: one with somatotropinoma [in 1/55 (1.8%)] and one with prolactinoma [in 1/25 (4%)]. None of the corticotrophinomas revealed gene alterations. Thus, the overall prevalence of variation was 2.1% in our cohort. Germline gene variations among Turkish patients with apparently sporadic PAs are relatively rare among patients ≤40 years old. None of the patients in our cohort revealed any obviously pathogenic variants.