MKRN3 Mutations in Central Precocious Puberty: A Systematic Review and Meta-Analysis

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Mutations in the MKRN3 gene are the most frequent genetic cause of central precocious puberty (CPP).
• Limited exploration exists regarding genotype-phenotype correlations for MKRN3 mutations in CPP.
• Understanding these associations is crucial for accurate diagnosis and management of CPP.

Purpose of the Study:

• To systematically review and analyze genotype-phenotype associations of MKRN3 mutations in CPP.
• To determine the prevalence of MKRN3 mutations in patients diagnosed with CPP.
• To investigate potential sex-dimorphic manifestations and demographic variations in mutation prevalence.

Main Methods:

• A systematic literature search was conducted across seven electronic databases up to September 4, 2018.
• Included studies evaluated MKRN3 mutations in patients with CPP, encompassing 22 studies and 880 subjects.
• Quantitative analysis involved 14 studies with 857 patients for pooled prevalence estimation.

Main Results:

• MKRN3 mutations were identified in 89 subjects (76 girls), associated with nonsyndromic CPP.
• Girls exhibited significantly earlier pubertal onset, higher basal FSH levels, and greater bone age advancement compared to boys.
• The pooled prevalence of MKRN3 mutations in CPP was 9.0%, with higher rates observed in males, familial cases, and non-Asian populations.

Conclusions:

• MKRN3 mutations are a common cause of nonsyndromic CPP, presenting with distinct sex-dimorphic features.
• Girls experience earlier pubertal onset due to MKRN3 mutations.
• These mutations are particularly prevalent in Western countries, especially among boys and in familial CPP cases.