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

Esin Karakilic-Ozturan; Volkan Karaman; Asuman Gedikbaşı; Şükran Poyrazoğlu; Feyza Darendeliler; Zehra Oya Uyguner; Firdevs Baş

doi:10.1177/20420188261424161

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

Ther Adv Endocrinol Metab. 2026 Feb 20:17:20420188261424161. doi: 10.1177/20420188261424161. eCollection 2026.

Authors

Esin Karakilic-Ozturan^{1

2}, Volkan Karaman³, Asuman Gedikbaşı⁴, Şükran Poyrazoğlu⁵, Feyza Darendeliler⁵, Zehra Oya Uyguner³, Firdevs Baş⁵

Affiliations

¹ Department of Pediatric Endocrinology and Diabetes, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Türkiye.
² Department of Pediatric Endocrinology and Diabetes, Kartal Dr. Lütfi Kirdar City Hospital, Istanbul 34865, Türkiye.
³ Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.
⁴ Department of Pediatric Basic Sciences, Institute of Child Health, Istanbul University, Istanbul, Türkiye.
⁵ Department of Pediatric Endocrinology and Diabetes, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.

Abstract

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.

Keywords: DLK1; MKRN3; central precocious puberty; serum level.