Misssense of KISS1 & Makorin in Central precocious Puberty
- Kokilavani K
- Jan 22, 2023
- 2 min read
Author: Kokilavani K (Msc Biochemistry)
LinkedIn: (https://www.linkedin.com/in/kokilavani-k-689ba618a/)
Making the protein known as makorin ring finger protein 3 is made possible by the MKRN3 gene (MKRN3). Puberty, which is defined as the changes in the body associated to sexual development that typically occur in adolescence which is directed by this protein. When hypothalamus is aroused, it releases spikes of a hormone called gonadotropin-releasing hormone, which marks the start of puberty (GnRH). According to research, the MKRN3 protein prevents (inhibits) the hypothalamus from releasing GnRH, delaying the start of puberty. Genomic imprinting is a process that results in gene activation differences particular to one or both parents. When related with this gene, the disorder can only be inherited from the father since only the copy of the MKRN3 gene from the father is activated. Both sons and daughters can experience central precocious puberty, but because puberty in girls begins even earlier than in boys, experts believe that girls are more seriously impacted than boys. Boys who have the MKRN3 gene mutation may reach puberty at the lower end of the usual age range, making the disorder difficult to identify.
The secretion of GnRH is actively inhibited during childhood and puberty begins by reactivating the secretion. Lack of GnRH leads to hypogonadotropic gonadism, in which patients do not develop puberty and are usually infertile. Conversely, early re-activation of GnRH secretion results in central early puberty
MKRN3 is an intron-less gene located on chromosome e15q11-q33. It is a maternally imprinted gene thus expressed only from the paternally inherited allele, coding for a zinc finger protein composed by 3 C3H1 zinc fingers, 1 motif rich in Cys and His residues and 1 C3H4 RING zinc finger. MKRN3 is a member of the makorin family of ubiquitin ligases and appears to have been acquired more recently than the other ubiquitin ligases.
MKRN3 protein structure and mutations identified in patients with central precocious puberty
GnRH is produced and secreted by the hypothalamus pulsatiles in the embryonic and neonatal phases of life. The secretion of GnRH is actively inhibited during childhood and puberty begins by reactivating the secretion. Lack of GnRH leads to hypogonadotropic gonadism, in which patients do not develop puberty and are usually infertile. Conversely, early re-activation of GnRH secretion results in central early puberty . Whilst several genes have been found in association with GnRH deficiency and have led to the current knowledge of GnRH regulation genes linked to CPP have until lately only been identified subsequent to their association with hypogonadotropic hypogonadism, such as KISS1 and KISS1R. Yet, only rare genetic defects in KISS1 and its receptor have been keyed out in patients with CPP.
Kisspeptin is a crucial regulator of human puberty and is encoded by the KISS1 gene Normosmic IHH is brought on by loss-of-function mutations in the kisspeptin receptor (GPR54 or KISS1R). Kisspeptin system involvement in the aetiology of sexual precocity has recently been discovered by an activating mutation of KISS1R with CPP. Kisspeptin is a potent stimulator of GnRH-induced gonadotropin production.
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