Novel MKRN3 Missense Mutations Associated With Central Precocious Puberty Reveal Distinct Effects on Ubiquitination
Authors' conclusion
MKRN3 mutations were present in 10.7% of our CPP cohort, consistent with previous studies. The novel identified mutations in different domains of MKRN3 revealed different patterns of ubiquitination, suggesting distinct molecular mechanisms by which the loss of MRKN3 results in early pubertal onset.
Study context
- Population
- Unrelated children with central precocious puberty (CPP) (79 girls, 5 boys) and, when available, their first-degree relatives; 5 academic medical institutions79 girls · 5 boys
- Participants
- 84 children
- Outcome
- MKRN3 and DLK1 mutations in CPP
Methodological detailsmulticentre
- Multicentre
Main finding
As reported in the abstract
- Heterozygous MKRN3 mutations identified, in 9 unrelated girls with CPP
- 8
- Novel missense MKRN3 mutations
- 5
- MKRN3 mutations previously identified in patients with CPP
- 2
- Frameshift variant not previously associated with CPP
- 1
- MKRN3 mutations present in CPP cohort
- 10.7%
Further findings
Clinical features: girls with vs without MKRN3 mutations
- Girls with MKRN3 mutations had earlier age of initial pubertal signs and higher basal serum LH and FSH than girls with CPP without MKRN3 mutations
Protein ubiquitination (Western blot) vs wild-type MKRN3
- Mutations within the RING finger domain reduced ubiquitination
- Mutations outside the RING finger domain increased ubiquitination
Original publication
Novel MKRN3 Missense Mutations Associated With Central Precocious Puberty Reveal Distinct Effects on Ubiquitination. J Clin Endocrinol Metab. Published 14 March 2023. doi:10.
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