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

MACEDO DB; MONTENEGRO LR; HUMMEL T; ABREU AP; KAISER UB; BESSA D; FRANÇA MM; SILVEIRA LG; BRASLAVSKY D; MENDONCA BB; BRITO VN; SILVA MC; BERGADÁ I; DAUBER A; LATRONICO AC

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2016

0028-3835

BACKGROUND/AIMS: Recently, loss-of-function mutations in the MKRN3 gene wereimplicated in the etiology of familial central precocious puberty (CPP) in bothsexes. We aimed to analyze the frequency of MKRN3 mutations in boys with CPP and to compare the clinical and hormonal features of boys with and without MKRN3mutations.METHODS: This was a retrospective review of clinical, hormonal and geneticfeatures of 20 male patients with idiopathic CPP evaluated at an academic medicalcenter. The entire coding regions of MKRN3, KISS1 and KISS1R genes weresequenced.RESULTS: We studied 20 boys from 17 families with CPP. All of them had normalbrain magnetic resonance imaging. Eight boys from 5 families harbored fourdistinct heterozygous MKRN3 mutations predicted to be deleterious for proteinfunction, p.Ala162Glyfs*14, p.Arg213Glyfs*73, p.Arg328Cys and p.Arg365Ser. Oneboy carried a previously described KISS1 activating mutation (p.Pro74Ser). Thefrequency of MKRN3 mutations among these boys with idiopathic CPP wassignificantly higher than previously reported female data (40 vs. 6.4%,respectively, p < 0.001). Boys with MKRN3 mutations had typical clinical andhormonal features of CPP. Notably, they had later pubertal onset than boyswithout MKRN3 abnormalities (median age 8.2 vs. 7.0 years, respectively, p =0.033).CONCLUSION: We demonstrated a high frequency of MKRN3 mutations in boys with CPP,previously classified as idiopathic, suggesting the importance of geneticanalysis in this group. The boys with CPP due to MKRN3 mutations had classicalfeatures of CPP, but with puberty initiation at a borderline age.