A novel heterozygous MKRN3 nonsense mutation in a Chinese girl with idiopathic central precocious puberty

Rationale: Central precocious puberty (CPP) is caused by the premature activation of the hypothalamic-pituitary-gonadal axis. Recently, the makorin ring finger protein 3 (MKRN3) mutations represent the most common genetic defects associated with CPP. However, the MKRN3 mutation is relatively rare in Asian countries. Here, we identified a novel heterozygous MKRN3 nonsense mutation (p. Gln363∗) causing CPP in a Chinese girl. Patient concerns: The index case is a 7-year-old Chinese girl who presented rapidly progressive precocious puberty with the onset of menstrual period 2 months after breast development, the advanced bone age (11 years), and the accelerated growth velocity (10 cm/year). Her basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, as well as the peak LH/FSH values after the gonadotropin-releasing hormone (GnRH) stimulation test were significantly elevated. Pelvic B ultrasound showed the presence of ovarian follicles with diameters ≥0.4 cm. Uterine length also indicated the onset of puberty. Contrast-enhanced magnetic resonance imaging (MRI) did not disclose any abnormality in the pituitary. Additionally, our present case was obese companies with impaired glucose tolerance (IGT) at the baseline assessment. Genetic analysis revealed a novel heterozygous nonsense mutation (c1087C>T; p. Gln363∗) in the maternally imprinted MKRN3, which inherited from the girl's father. Diagnosis: Combined with the symptoms, hormonal data, and the results of the pelvic B ultrasound, the girl was diagnosed as CPP. Interventions: The girl has been treated with a GnRH analog (3.75 mg every 4 wks) for 1 year and 5 months. Outcomes: The puberty signs have since not progressed during the follow-up period, which indicates that the GnRH analogs treatment is effective. Lessons: This case was obese companied with IGT at the baseline assessment and exhibited stronger LH/FSH response to GnRH stimulation test. Therefore, clinicians should highlight the importance of weight management and the long-term follow-up to monitor the adverse health outcomes, especially for the polycystic ovary syndrome in later life.