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

Abstract

Background: Caused by premature activation of the hypothalamic-pituitary-gonadal axis, there is increasing incidence of central precocious puberty (CPP), especially in girls. Makorin ring finger protein 3 (MKRN3), a maternal imprinted gene with a highly conserved sequence, is the most common genetic etiology associated with CPP. Approximately 50 different mutations in MKRN3 have been found in CPP.

Case summary: This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years. The left hand bone age of both patients revealed advanced age (9 years). Pelvic B ultrasound indicated enlargement of the ovaries. Luteinizing hormone (LH) releasing hormone testing confirmed CPP. Whole-exome sequencing detected the c.841C>T mutation in MKRN3, leading to a single base substitution, in the twins. This mutation was inherited from the father and paternal grandmother. After 3 mo of treatment with a gonadotropin-releasing hormone analog, levels of LH, follicle-stimulating hormone, and estradiol in the proband's sister returned to normal levels.

Conclusion: Here, we report a rare mutation (c.841C>T) in MKRN3 in identical twin sisters with CPP.

Keywords: Case report; Central precocious puberty; MKRN3; Mutation.

Figure 1

Pedigrees of the investigated case with MKRN3 mutation. Square indicates male family member, circles indicate female members, the black symbol indicates clinically affected family member, the symbol with black circle indicates unaffected carrier, arrow indicates the proband, the arrow indicates the profound in this family.

Figure 2

Whole-exome sequencing showing the novel heterozygous mutation (c.841 C>T) in MKRN3 detected in the profound. The same mutation was covered in A’s twin sister, her father and grandmother, but not A’s mother.