High Frequency of MKRN3 Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic

MENDONCA, BERENICE B.; LATRONICO, ANA CLAUDIA; DAUBER, ANDREW; BRASLAVSKY, DEBORA; KAISER, URSULA B.; BERGADÁ, IGNACIO; SILVEIRA, LETICIA G.; ABREU, ANA PAULA; CUNHA-SILVA, MARINA; FRANÇA, MONICA M.; HUMMEL, TIAGO; BRITO, VINICIUS N.; MONTENEGRO, LUCIANA R.; BESSA, DANIELLE S.; MACEDO, DELANIE B.

NEUROENDOCRINOLOGY

KARGER

Año: 2018 vol. 105 p. 17 - 25

0028-3835

Background/Aims?Recently, loss-of-function mutations in the MKRN3 gene have beenimplicated in the etiology of familial central precocious puberty (CPP) in both sexes. We aimed toanalyze the frequency of MKRN3 mutations in boys with CPP and to compare the clinical andhormonal features of boys with and without MKRN3 mutations.Methods?This was a retrospective review of clinical, hormonal and genetic features of 20 malepatients with idiopathic CPP evaluated at an academic medical center. The entire coding regions ofMKRN3, KISS1 and KISS1R genes were sequenced.Results?We studied 20 boys from 17 families with CPP. All of them had normal brain magneticresonance imaging. Eight boys from 5 families harbored four distinct heterozygous MKRN3mutations predicted to be deleterious for protein function, p.Ala162Glyfs * 14, p.Arg213Glyfs *73, p.Arg- 328Cys and p.Arg365Ser. One boy carried a previously described KISS1-activatingmutation (p.Pro74Ser). The frequency of MKRN3 mutations among these boys with idiopathicCPP was significantly higher than previously reported female data (40 vs. 6.4%, respectively, p