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We agree that assessing the initiation of male puberty can be a challenge and that central precocious puberty in males is often underdiagnosed. However, we are aware of the importance of the results we have reported recently. The reason we did not provide additional clinical and hormonal data for the initiation of pubertal development is that this period had to be evaluated retrospectively in both males with paternally inherited MKRN3 mutations. In our paper, we stated the age at starting facial shave in asymptomatic males. The interval between testicular enlargement (Tanner stage 2) and need for regular shaving (Tanner stage 5) is between 4 and 5 years in the general population. It is about 4.3 years in Bulgarian boys.1Stanimirova N. Peneva L. Baltova T. Physical and pubertal development of Bulgarian children.1st ed. 2007Google Scholar Therefore, we do not suspect the presence of premature pubertal signs in a man who started shaving at the age of 15 years. Final height is also important for the assessment of pubertal development and it is normal in both reported males. The height of the carrier of mutation p.Pro161Argfs*10 is 171.5 cm; his mid-parental height is 173.7 cm. The carrier of the novel mutation (p.Arg351Serfs*44) is 177 cm; his mid-parental height is 177.2 cm. This novel frameshift mutation is associated with early onset and fast progression of pubertal signs in our female patient with central precocious puberty. The exact mechanisms, by which the gene MKRN3 and its product influence human puberty, are not clear. A few studies in patients with central precocious puberty show that MKRN3 mutations affect girls more severely than boys.2Settas N. Dacou-Voutetakis C. Karantza M. Kanaka-Gantenbein C. Chrousos G.P. Voutetakis A. Central precocious puberty in a girl and early puberty in her brother caused by a novel mutation in the MKRN3 gene.J Clin Endocrinol Metab. 2014; 99: E647-51Crossref PubMed Scopus (65) Google Scholar, 3Känsäkoski J. Raivio T. Juul A. Tommiska J. A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty.Pediatr Res. 2015; 78: 709-711Crossref PubMed Scopus (33) Google Scholar, 4Bessa D.S. Macedo D.B. Brito V.N. França M.M. Montenegro L.R. Silva M.C. et al.High frequency of MKRN3 mutations in male central precocious puberty previously classified as idiopathic.Neuroendocrinology. 2016; (May 26. [Epub ahead of print])PubMed Google Scholar Having in mind this sex difference, it is not so unexpected for us that some males might not develop the disease. Underdiagnosis of central precocious puberty in boys with loss-of-function mutations of MKRN3The Journal of PediatricsVol. 183PreviewThe determination of age at pubertal onset in boys can be a challenge, because testicular enlargement (first male pubertal sign) is not as obvious as thelarche and menarche in girls. Male patients usually remember only late events of puberty, such as the age at initiation of full facial shaving and the age at voice change. In 2013, we first demonstrated that loss-of-function mutations of MKRN3, an imprinted gene at chromosome 15q11.2, cause central precocious puberty (CPP) in both sexes.1 Autosomal-dominant inheritance and complete penetrance have been demonstrated in all subsequently reported families with CPP owing to MKRN3 defects. Full-Text PDF