| Autor: |
Tuncer FN; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey., Çiftçi Doğanşen S; Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.; Division of Endocrinology and Metabolic Diseases, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey., Serbest E; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey., Tanrıkulu S; Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.; Division of Endocrinology and Metabolic Diseases, Haydarpaşa Numune Training and Research Hospital, Istanbul, Turkey., Ekici Y; Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey., Bilgiç B; Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Yarman S; Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. |
| Abstrakt: |
Aims: Aryl hydrocarbon receptor-interacting protein ( AIP ) 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 AIP 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. Materials and Methods: A total of 97 patients, diagnosed with functional PAs ≤40 years old, composed of somatotropinoma ( n = 55), prolactinoma ( n = 25), and corticotrophinoma ( n = 17), were recruited for this study. Fifty-one of these patients [somatotropinoma ( n = 30), prolactinoma ( n = 15), and corticotrophinoma ( n = 11)] were previously reported as AIP mutation-negative by Sanger sequencing. The entire coding sequence of the AIP 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 AIP gene. Results: The AIP 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 AIP gene alterations. Thus, the overall prevalence of AIP variation was 2.1% in our cohort. Conclusions: Germline AIP 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 AIP variants. |
