Serum MKRN3 levels in girls with central precocious puberty due to MKRN3 loss-of-function mutation

Macena Larissa Baracho; Piovesan Maiara Ribeiro; Bastos Aline Almeida; Pedrosa Ludmila Fernandes; Montenegro Luciana Ribeiro; Machado Canton Ana Pinheiro; Valassi Helena Pantaleiou; Mendonca Berenice Bilharinho; Latronico Ana Claudia; Brito Vinicius Nahime

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ESPE Abstracts (2024) 98 P2-240

ESPE2024 Poster Category 2 Pituitary, Neuroendocrinology and Puberty (36 abstracts)

Serum MKRN3 levels in girls with central precocious puberty due to MKRN3 loss-of-function mutation

Larissa Baracho Macena ¹ , Maiara Ribeiro Piovesan ^1,2 , Aline Almeida Bastos ¹ , Ludmila Fernandes Pedrosa ¹ , Luciana Ribeiro Montenegro ^1,3 , Ana Pinheiro Machado Canton ¹ , Helena Pantaleiou Valassi ² , Berenice Bilharinho Mendonca ^1,2 , Ana Claudia Latronico ¹ & Vinicius Nahime Brito ^1,2

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¹Division of Endocrinology and Metabology, Clínicas Hospital, Faculty of Medicine of USP, Faculty of Medicine of USP, São Paulo, Brazil. ²Laboratory of Hormones and Molecular Genetics LIM 42 Clínicas Hospital, Faculty of Medicine of USP, Sao Paulo, Brazil. ³Hormone and Molecular Genetics Laboratory LIM 25. Clínicas Hospital, Faculty of Medicine of USP, Faculty of Medicine of USP, Paulo, Brazil

Background: MKRN3 is known to decline prior to pubertal development in healthy individuals, indicating a potential inhibitor effect on reproductive axis. Currently, MKRN3 loss-of-function mutations represent the main genetic cause of familial central precocious puberty (CPP) in both sexes. The impact of these mutations on MKRN3 serum levels is poorly understood.

Aim: To assess serum MKRN3 levels in girls with CPP due to MKRN3 mutations.

Patients and Methods: Seven girls with CPP due to MKRN3 mutations were studied. Four unrelated girls harbored MKRN3 mutations in the coding region and three girls from two unrelated families (including a pair of siblings, and one girl from another family) in the promoter region of MKRN3. Serum MKRN3 levels were assessed by a manual enzyme- immunoassay (ELISA- My biosource). All samples were assessed in duplicate, analytical sensitivity was 10 pg/mL, with working range from 62.5 – 2.000 pg/mL. Intra-assay variation was <15%.

Results: Serum MKRN3 levels ranged from 197.5 to 1434.7 pg/mL in all girls. In the four girls carrying mutations in the coding region (p.Ala162Glys*15 in three girls and p.Pro161Argfs*10 in one girl), mean serum MKRN3 levels were 995.02 ± 373.85 pg/mL, ranging from 554 to 1434.7 pg/mL, whereas in the three girls with allelic variant in the promoter region (c.-265G>A) the mean serum MKRN3 was 470.83 ± 237.02 pg/mL, ranging from 197.5 to 619.6 pg/mL. Although the mean serum values of MKRN3 in girls with promoter region mutations were lower, there was no statistical significant difference compared with the group with MKRN3 mutations in the coding region (P = 0.07)

Conclusion: MKRN3 loss-of-function mutations did not exhibit a consistent pattern of influence on serum levels, resulting in wide variation.