ESPE Abstracts

Introduction: Loss-of-function mutations in genomically imprinted MKRN3 and DLK1 genes cause familial central precocious puberty (CPP) and may result in low serum concentrations of these proteins. This study aimed to evaluate the predictive value of serum MKRN3 and DLK1 concentrations for detecting variants in related genes.

Material-Method: This retrospective study included 26 girls with CPP, of which 11 were receiving GnRH analog(a) therapy (Group-1), while the others had not yet been treated (Group-2). The control group consisted of 26 healthy girls. The serum concentrations of MKRN3 and DLK1 were measured by ELISA, and MKRN3 and DLK1 genes were performed by Sanger sequence. Statistical analysis was performed using the Jamovi package program (version 2.3).

Results: In Group-1, the median (IQR) age was 7.6(1.1) years, with height and BMI-SDS of +1.4 (1.5) and +0.8 (0.7), respectively. In Group-2, the median age was 7.9 (0.7) years, with height and BMI-SDS of +1.6 (1.1) and +0.4(1.4), respectively. In the control group, the median age was 7.1(1.4) years, with height and BMI-SDS of 0.7(1.4) and -0.01(1.9), respectively. In Group-1, a known pathogenic c.482dupC/p.(Ala162Glyfs*15) variant in the MKRN3 gene was detected in one patient, whose serum MKRN3 concentration was 0.127 ng/mL. The median MKRN3 and DLK1 serum concentrations of patients other than the case with the variant detected in Group-1 were 1.32 (0.7) ng/mL and 0.62 (0.4) ng/mL, respectively. In Group-2, these concentrations were 1.2 (0.6) ng/mL and 0.62 (0.2) ng/mL, respectively. There was no statistically significant difference in serum concentrations between Group-1 and Group-2 (P=0.279; P=0.338). In the control group, mean±SD serum concentrations of MKRN3 and DLK1 were 1.31±0.5 and 0.81±0.4, respectively. When the control group was compared with the whole group, except for the case with the variant, no difference was found between the concentrations (P=0.917; P=0.674).

Conclusion: MKRN3 and DLK1 serum concentrations are not significantly different between CPP patients receiving GnRHa therapy, those not yet treated, and the control group. However, a known variant in the MKRN3 gene was detected in a patient with a significantly low serum MKRN3 concentration. This highlights the potential utility of serum concentration measurement in detecting variants in the related gene. Moreover, it is essential to note that variants in these genes can be familial, even in individuals without a family history, due to the paternal inheritance pattern, and family segregation studies should be performed.