Predicting MKRN3 and DLK1 Variants Using Serum Levels in Precocious Puberty

Purpose Loss-of-function alterations in MKRN3 and DLK1 are linked to familial central precocious puberty (CPP) and may lower serum protein levels. This study assessed whether serum MKRN3 and DLK1 levels indicate CPP-related genetic variants. Methods Twenty-six girls with CPP—11 treated (Group 1) and 15 untreated (Group 2)—and 26 healthy controls were enrolled. Serum MKRN3 and DLK1 were measured using ELISA; genes were analyzed by Sanger sequencing. Results One patient had a known pathogenic MKRN3 variant (c.482dupC/p.(Ala162Glyfs*15)) and very low MKRN3 level (0.127 ng/mL), consistent with paternal inheritance. Excluding this case, median MKRN3 and DLK1 levels were 1.32 (0.7) ng/mL and 0.62 (0.4) ng/mL in Group 1, and 1.2 (0.6) ng/mL and 0.62 (0.2) ng/mL in Group 2. Controls had median MKRN3 and DLK1 levels of 1.177 (0.76) ng/mL and 0.67 (0.44) ng/mL, respectively. No significant differences were observed between groups (MKRN3: p = 0.279, p = 0.917; DLK1: p = 0.338, p = 0.756). Conclusion Although MKRN3 and DLK1 levels did not significantly differ, the case with a pathogenic MKRN3 variant and low MKRN3 level suggests that serum measurements may help in detecting such variants. Familial studies are recommended as these variants may be inherited even in isolated cases.