ESPE Abstracts (2016) 86 P-P1-752

A Novel MKRN3 Frameshift Mutation in a Bulgarian Girl with Central Precocious Puberty

Mihaela Dimitrovaa,b, Elisaveta Stefanovaa,b, Maria Glushkovab,c, Albena Todorovab,c, Tihomir Todorovc, Maia Konstantivaa,b, Krasimira Kazakovaa,b & Radka Tinchevaa,b


aDepartment of Endocrinology and Genetics, University Children’s Hospital, Sofia, Bulgaria; bMedical University Sofia, Sofia, Bulgaria; cGenetic Medico-Diagnostic Laboratory Genica, Sofia, Bulgaria


Background: Precocious puberty is defined as the onset of pubertal signs in girls younger than 8 years of age and in boys younger than 9 years of age. Central precocious puberty is due to an early activation of the hypothalamic-pituitary-gonadal axis. Different candidate genes were involved in the etiology of the disease. To date, mutations in the maternally imprinted gene MKRN3 are most frequently found in families with CPP.

Objective and hypotheses: The aim of our study was to search for mutations in MKRN3 in cases of sporadic CPP.

Method: We screened 10 Bulgarian girls diagnosed with idiopathic CPP for mutations in MKRN3.

Results: Heterozygous mutations in the MKRN3 gene were detected in two girls – one novel frameshift mutation (p.Arg351Serfs*44) and a previously reported one (p.Pro161Argfs*10). Genetic testing of the members of the two families revealed the paternal origin of the detected mutations. Two of the males with paternally inherited MKRN3 mutations did not have early activation of hypothalamic-pituitary-gonadal axis.

Conclusion: We report a novel mutation in gene MKRN3 (p.Arg351Serfs*44) with a very probable deleterious effect in a girls with CPP. Although paternally inherited MKRN3 mutations are responsible for CPP in females, it seems that they do not necessarily lead to precocious pubertal development in males. We assume that this is due to any of the epigenetic mechanisms involved in gene expression control, particularly in this 15q11-q13.3 critical region.

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