Genotype–phenotype associations of MKRN 3 variants in children with central precocious puberty: a single-center study from Uzbekistan

Abstract Objectives To determine the frequency of selected MKRN3 variants and to investigate genotype–phenotype associations in Uzbek children with central precocious puberty, with particular emphasis on sex-specific clinical, hormonal, and instrumental characteristics. Methods This single-center study included 69 Uzbek children with CPP and 30 healthy controls (used primarily for assay validation). Targeted genotyping of three MKRN3 variants (c.1034G>A [p.Arg345His], c.1229G>A [p.Cys410Ter], and c.331G>T [p.Glu111Ter]) was performed using real-time PCR with TaqMan assays. Clinical, hormonal, skeletal, and ultrasonographic parameters were analyzed using non-parametric methods. Results Selected MKRN3 variants were identified in 21.7 % (15/69) of this cohort of Uzbek children with CPP. The most frequent variant was c.1034G>A (13.0 %), followed by c.1229G>A (8.7 %); c.331G>T was not detected. Variant frequency was higher in boys (28.6 %) than in girls (18.7 %), without statistical significance. In girls, variant carriers had significantly smaller uterine and ovarian dimensions, larger dominant follicle diameter, and lower basal LH levels, while bone age advancement and estradiol levels were comparable. In boys, variant carriers demonstrated higher testosterone levels, with no significant differences in gonadotropins, bone age advancement, or testicular volume. Conclusions Selected MKRN3 variants were present in 21.7 % of this cohort of Uzbek children with CPP. MKRN3 -related CPP demonstrated genotype-specific morphological and endocrine features, particularly in girls. These findings suggest phenotypic heterogeneity and warrant confirmation in larger sequencing-based studies.