Phenocopies of multiple endocrine neoplasia type 1: role of the genes, associated with the development of pituitary adenomas

Background. Absence of detectable MEN1 mutations in a patient with multiple endocrine neoplasia type 1 (MEN1) phenotype may disprove the hereditary predisposition and the necessity of a lifelong regular screening for detecting the remaining components of the syndrome, and the examination of the first-degree relatives. Nevertheless, there may be other genes involved in the co-occurrence of several MEN1-associated tumors. 

Aim — to determine the role of genes, associated with the development of familial pituitary adenomas (PA), and genes, presumably involved in pathogenesis of sporadic PA, in the development of MEN1 phenocopies with PA as one of components.

Material and methods. 23 patients with MEN1 phenocopy were included in the study. The patients underwent next-generation sequencing (NGS) (Ion TorrentTM PGMTM, Thermo Fisher Scientific — Life Technologies, USA) using a panel of candidate genes (MEN1, CDKN1B, PRKAR1A, AIP, SDHA, SDHB, SDHC, SDHD, GNAS, PRKCA, CDKN2A, CDKN2C, POU1F1, PTTG2).

Results. In 1 (4%) female patient with acromegaly and primary hyperparathyroidism (PHPT) a germline heterozygous change in exon 6 of AIP gene c.911G>A (p.R304Q) was revealed. In four female patients with acromegaly and PHPT we revealed polymorphisms whose pathological significance is not defined: heterozygous change in exon 1 of PTTG2 gene c.134G>A (p.R45H), heterozygous change in intron 1 of PRKAR1A gene (c.–10G>C), heterozygous change in exon 5 of SDHB gene c.487T>C (p.S163P), heterozygous change in 3’-UTR of CDKN1B gene g.3897G>T (c*8G>T).

Conclusions. The results of our study show that mutations in the majority of the examined genes associated with the development of hereditary and sporadic PA, do not cause the development of MEN1 phenocopies. The necessity to study AIP gene in all patients with MEN1 phenocopies needs further research. It is recommended to search for new genes, mutations in which could be the cause of the development of MEN1 phenocopies.

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