Endocrine Abstracts

Background: Nowadays, single nucleotide polymorphisms in genes KISS1, KISS1R, MKRN3, DLK1 have been described as the leading cause of precocious hypothalamic-pituitary axis activation in children. Genetic testing in patients with hereditary forms of precocious puberty (PP) can expand our knowledge in underlying molecular mechanisms of the disease. The diagnosis of genetic bases is necessary for genetic counselling.

Aim: To access clinical characteristics and define genetic defects in patients with hereditary forms of gonadotropin-dependent precocious puberty.

Materials and Methods: 21 patients with positive family history were enrolled into the study: 8 patients were with paternal disease history, 6 – with maternal. 7 patients had siblings with diagnosed PP. The full-exome sequencing was conducted in all the patients.

Results: The median of patients age at the time of the examination was 7,2 years [6,5; 7,7]. Single nucleotide variants were identified in 13 (62%) of patients. MKRN3 gene defects were the most common: 10 out of 13 patients had defect in this gene. The rest of the group had defects in genes associated with neuroontogenesis and neuroendocrine regulation mechanisms of hypothalamic-pituitary axis: MAPK8IP3 (OMIM no. 605431), POU1F1 (OMIM no. 173110) and NPFF1R (OMIM no. 607448).

Conclusion: MKRN3 defects are the most common genetic cause of hereditary forms of gonadotropin-dependent PP which is consistent with worldwide data.