Rare mutation in MKRN3 in two twin sisters with central precocious puberty: Two case reports

Area of Science:

• Pediatric Endocrinology
• Genetics
• Reproductive Medicine

Background:

• Central precocious puberty (CPP) incidence is rising, particularly in girls, due to early activation of the hypothalamic-pituitary-gonadal axis.
• Mutations in the maternal imprinted gene Makorin ring finger protein 3 (MKRN3) are the most frequent genetic cause of CPP.
• Over 50 MKRN3 mutations have been identified in patients with CPP.

Observation:

• This report details identical twin sisters who presented with premature thelarche at age six.
• Diagnostic evaluations included advanced bone age (9 years), enlarged ovaries on pelvic ultrasound, and confirmed CPP via LHRH testing.
• Whole-exome sequencing identified a novel c.841C>T mutation in the MKRN3 gene in both twins, inherited paternally.

Findings:

• A rare c.841C>T mutation in the MKRN3 gene was identified in identical twin sisters diagnosed with CPP.
• This specific mutation, leading to a single base substitution, was confirmed to be paternally inherited.
• Treatment with a GnRH analog normalized hormone levels (LH, FSH, estradiol) in one twin after three months.

Implications:

• This case expands the spectrum of known MKRN3 mutations associated with CPP.
• It underscores the importance of genetic testing for MKRN3 in cases of CPP, even in familial contexts.
• Understanding MKRN3 mutations aids in diagnosing and managing CPP, potentially improving treatment strategies.