Genetic causes of central precocious puberty

Area of Science:

• Endocrinology
• Genetics
• Reproductive Medicine

Background:

• Central precocious puberty (CPP) involves premature activation of the hypothalamus-pituitary-gonadal axis.
• While organic brain lesions can cause CPP, idiopathic forms are linked to genetic and environmental factors.
• Genetic abnormalities in genes like KISS1R, KISS1, MKRN3, DLK1, and PROKR2 have been identified as causes of CPP.

Purpose of the Study:

• To review the genetic underpinnings of idiopathic and familial central precocious puberty.
• To highlight the role of specific genes, such as MKRN3 and DLK1, in the etiology of CPP.
• To underscore the importance of understanding genetic mechanisms in puberty and reproduction.

Main Methods:

• Literature review of genetic studies on central precocious puberty.
• Analysis of reported genetic variants in genes associated with CPP.
• Examination of the prevalence and inheritance patterns of CPP-related genetic mutations.

Main Results:

• Mutations in KISS1R were first identified as a cause of idiopathic CPP in 2008.
• MKRN3 exhibits the highest frequency of pathological variants globally, though rare in East Asian populations.
• MKRN3 and DLK1 are maternal imprinting genes; CPP arises from paternal inheritance of pathogenic variants, potentially by negatively regulating puberty progression.

Conclusions:

• Genetic factors play a significant role in the development of central precocious puberty.
• Understanding the genetics of CPP, particularly imprinting genes like MKRN3 and DLK1, is crucial for elucidating puberty regulation.
• Further research into the genetics of CPP is anticipated to advance our knowledge of reproductive mechanisms.