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MKRN3 circulating levels in Prader–Willi syndrome: a pilot study

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Abstract

Context

Hypogonadism in Prader–Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect. MKRN3, a maternal imprinted gene located on 15q11.2-q13 region, encodes makorin ring finger protein 3, whose deficiency causes precocious puberty, an extremely rare symptom in PWS.

Objective

This study aimed to evaluate MKRN3 levels in patients with PWS and to analyze its correlation with sexual hormone levels, insulin resistance and Body Mass Index (BMI).

Methods

We performed an observational cross-sectional study and enrolled 80 patients with genetically confirmed diagnosis of PWS with median age of 9.6 years.

Results

MKRN3 levels were measurable in 49 PWS patients with a geometric mean of 34.9 ± 22 pg/ml (median: 28.4). Unmeasurable levels of MKRN3 were found in 31 patients. No statistically significant differences were found between patients with and without measurable MKRN3 levels for any clinical, biochemical, or genetic characteristics. However, MKRN3 levels were inversely correlated with HOMA-IR index (p: 0.005) and HbA1c (p: 0.046) values. No statistically significant correlations were found between MKRN3 and LH, estradiol and testosterone concentrations, pubertal development and genetic defect, whereas a direct correlation with FSH was found (p: 0.007).

Conclusions

The typical genetic defect of PWS should lead to unmeasurable levels of the MKRN3 protein due to the inactivation of the paternal allele. Measurable circulating MKRN3 could suggest the possible involvement of tissue-specific imprinting mechanisms and other regulatory factors in gene expression. Correlations with HOMA-IR index, HbA1c, and FSH suggest peripheral actions of MKRN3, but future studies are warranted to investigate this topic.

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Acknowledgements

We thank all the families of patients included in the study for the support and participation.

Funding

This work was supported by a grant (390) funded by “VALERE: VAnviteLli pEr la RicErca” program of University of Campania “L. Vanvitelli”.

Author information

Authors and Affiliations

  1. Endocrinology Unit, University Pediatric Department, Bambino Gesù Children’s Hospital, Piazza S.Onofrio, 4, 00165, Rome, Italy

    M. Mariani, D. Fintini, S. Bocchini & M. Cappa

  2. Department of Woman, Child, General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy

    G. Cirillo, S. Palumbo, E. M. del Giudice & A. Grandone

  3. Research Area for Multifactorial Diseases and Complex Phenotypes, Bambino Gesù Children’s Hospital, Rome, Italy

    M. Manco

Authors
  1. M. Mariani
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  2. D. Fintini
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  3. G. Cirillo
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  4. S. Palumbo
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  5. E. M. del Giudice
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  6. S. Bocchini
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  7. M. Manco
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  8. M. Cappa
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  9. A. Grandone
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Corresponding author

Correspondence to M. Mariani.

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Conflict of interest

The authors have no conflicts of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of the “Bambino Gesù” Children’s Hospital (No 2092/2020).

Informed consent

The written informed consent of the parents of all enrolled patients was collected and is in our possession.

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Mariani, M., Fintini, D., Cirillo, G. et al. MKRN3 circulating levels in Prader–Willi syndrome: a pilot study. J Endocrinol Invest 45, 2165–2170 (2022). https://doi.org/10.1007/s40618-022-01860-0

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  • DOI: https://doi.org/10.1007/s40618-022-01860-0

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