Use of serum MKRN3 and DLK1 levels in precocious puberty: association with an MKRN3 pathogenic variant.

BACKGROUND

Loss-of-function alterations in Makorin Ring Finger Protein 3 (MKRN3) and Delta-like Non-Canonical Notch Ligand 1 (DLK1) genes are associated with familial central precocious puberty (CPP) and can result in reduced serum levels of these proteins.

OBJECTIVES

This study aimed to evaluate the potential of serum MKRN3 and DLK1 levels for predicting genetic variants associated with CPP.

DESIGN

Retrospective study.

METHODS

This retrospective cross-sectional study included 26 girls with CPP: 11 receiving treatment (Group 1) and 15 not yet treated (Group 2). The control group consisted of 26 healthy girls. Serum MKRN3 and DLK1 levels were measured by ELISA, and MKRN3 and DLK1 genes were analyzed by Sanger sequencing.

RESULTS

A known pathogenic MKRN3 gene variant (c.482dupC/p.(Ala162Glyfs*15)) was found in one patient with a notably low MKRN3 level of 0.127 ng/mL, consistent with paternal inheritance. Median MKRN3 and DLK1 levels were 1.32 (0.7) and 0.62 (0.4) ng/mL in Group 1, and 1.2 (0.6) and 0.62 (0.2) ng/mL in Group 2 (excluding the patient with the variant). No significant differences were observed between Group 1 and Group 2 (p = 0.279; p = 0.338). Control group median serum levels were 1.177 (0.76) ng/mL for MKRN3 and 0.67 (0.44) ng/mL for DLK1, with no significant differences from the CPP cohort (p = 0.917; p = 0.756).

CONCLUSION

MKRN3 and DLK1 levels do not significantly differ between treated, untreated CPP patients, and healthy controls. Identifying a known MKRN3 variant with low serum levels suggests serum measurements can help predict variants. Familial studies are recommended as these variants may be inherited even in isolated cases.