A novel MKRN3 nonsense mutation causing familial central precocious puberty

Excerpt

Central or gonadotropin-dependent precocious puberty (CPP) caused by early activation of pulsatile Gonadotropin-releasing hormone (GnRH) secretion is clinically defined by the early maturation of the entire hypothalamic-pituitary-gonadal axis and the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys [1]. Pubertal timing and growth are influenced by complex interactions of genetic, nutritional, environmental, and socioeconomic factors [2]. Epidemiological studies suggest that around 60–80% of the variation in pubertal onset might be genetically determined [3]. Additionally, family history of CPP has been identified in up to 27.5% of cases with an autosomal mode of inheritance [4]. To date, only a handful of genes, involving both the excitatory and the inhibitory pathways of GnRH secretion, have been reported as causative for CPP and mutations were identified in the kisspeptin system - kisspetin 1 (KISS1) and its receptor (KISS1R) [5, 6], and in the makorin RING-finger protein 3 (MKRN3) gene [7]. The initial report by Abreu et al. [7], describing 3 MKRN3 gene frameshift mutations predicted to encode truncated proteins and one missense mutation predicted to disrupt protein function in 2013, was followed by a few more reports of novel loss-of-function mutations resulted to MKRN3 protein deficiency and premature initiation of puberty [8‐16]. …