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. 2020 Mar 30;46(1):39.
doi: 10.1186/s13052-020-0808-6.

MKRN3 and KISS1R mutations in precocious and early puberty

Sara Pagani  1 , Valeria Calcaterra  1 , Gloria Acquafredda  2 , Chiara Montalbano  1 , Elena Bozzola  3 , Pietro Ferrara  4 , Manuela Gasparri  5 , Alberto Villani  3 , Mauro Bozzola  6
Affiliations

MKRN3 and KISS1R mutations in precocious and early puberty

Sara Pagani et al. Ital J Pediatr. .

Abstract

Background: Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of KISSR1 (previously named GPR54) and MKRN3 genes on pubertal timing.

Methods: We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8 years of age, and in 6 girls affected by early puberty (EP) between 8 and 10 years of age.

Results: Direct sequencing of the KISS1R (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the GPR54 gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of MKRN3 in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3/13 CPP patients and 3/6 EP patients) we found the synonymous variant c.663C > T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient.

Conclusion: In conclusion, we identified sequence variations of the KISS1R and MKRN3 genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP.

Keywords: Early onset of puberty; Genetic variations; Growth factors; MKRN3 and KISS1R genes; Precocious puberty.

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Conflict of interest statement

The authors declare that they have no competing interests.

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References

    1. Rhie JY, Lee KH, Ko JM, Lee WJ, Kim JH, Kim HS. KISS1 gene polymorphisms in Korean girls with central precocious puberty. J Korean Med Sci. 2014;29:1120–1125. doi: 10.3346/jkms.2014.29.8.1120. - DOI - PMC - PubMed
    1. Simsek E, Demiral M, Ceylaner S, Kirel B. Two frameshift mutations in MKRN3 in Turkish patients with familial central precocious puberty. Horm Res Paediatr. 2017;87:405–411. doi: 10.1159/000450923. - DOI - PubMed
    1. Aycan Z, Savas-Erdeve S, Cetinkaya S, Kurnaz E, Keskin M, Sahin NM, et al. Investigation of MKRN3 mutation in patients with familial central precocious puberty. J Clin Res Pediatr Endocrinol. 2018;10:223–229. doi: 10.4274/jcrpe.5506. - DOI - PMC - PubMed
    1. Teles MG, Bianco S, Brito VN, Trarbach EB, Kuohung W, Xu S, et al. A GPR54 activating mutation in a patient with central precocious puberty. N Engl J Med. 2008;358:709–715. doi: 10.1056/NEJMoa073443. - DOI - PMC - PubMed
    1. Silveira LG, Noel SD, Silveira-Neto AP, Abreu AP, Brito VN, Santos MG, et al. Mutations of the KISS1 gene in disorders of puberty. J Clin Endocrinol Metab. 2010;95:2276–2280. doi: 10.1210/jc.2009-2421. - DOI - PMC - PubMed