ESPE Abstracts

Background: Central precocious puberty (CPP) is often familial but its genetic cause is largely unknown. Very recently, the makorin RING finger protein 3 (MKRN3) gene, located on chromosome 15 in the Prader-Willi syndrome (PWS)-associated region (15q11-q13), has been found mutated for the first time in five families with familial precocious puberty, with a peculiar kind of transmission. In fact, it is an imprinted gene which is expressed only if transmitted from the father. The function of this gene is not completely known and the phenotype of patients with mutations in MKRN3 gene is not yet completely elucidated. We report a new mutation (Pro160Cysfs*14) in the paternally imprinted MKRN3 gene causing familial CPP.

Case presentation: When the index case, a 7 years old girl, came to our observation, showed Tanner stage 3 and pubic hair stage 1. Her bone age evaluated by TW2 method was 10.3 years. Her laboratory data confirmed diagnosis of central precocious puberty. Familial medical history revealed precocious puberty in a cousin on paternal side and in her paternal grandmother. Genetic analysis revealed a new mutation (Pro160Cysfs*14) in the paternally imprinted MKRN3. Puberty onset was at about 6 years in all affected female family members and the grandmother presented also premature menopause. Precocious puberty was well controlled by pharmacological therapy.

Conclusion: We highlight the importance of an accurate family medical history to disclose the peculiar pattern of inheritance of this gene and add new data to knowledge of the phenotype of MKRN3 mutations. We expand the phenotypic knowledge of mutations of this gene reporting an affected family member with both early menarche and premature menopause.