Comprehensive Study on Central Precocious Puberty: Molecular and Clinical Analyses in 90 Patients

Area of Science:

• Pediatric Endocrinology
• Genetics
• Reproductive Medicine

Background:

• Central precocious puberty (CPP) can result from defects in genes like MKRN3, DLK1, KISS1, KISS1R, and disorders such as Temple syndrome (TS14).
• Recent studies suggest pathogenic variants in MECP2 may also contribute to CPP.

Purpose of the Study:

• To investigate the contribution of genetic and epigenetic abnormalities to CPP.
• To analyze the clinical and hormonal features associated with different etiologies of CPP.

Main Methods:

• Targeted sequencing of MKRN3, DLK1, MECP2, KISS1, and KISS1R in 90 CPP patients.
• Methylation analysis for imprinting disorders like TS14.
• Measurement of serum DLK1 and MKRN3 levels in specific patient groups and controls.

Main Results:

• Identified 8 patients with TS14 (epimutation, UPD14, microdeletion) and 3 with MKRN3 defects (PV, 5'-UTR deletion, microdeletion).
• No pathogenic variants were found in MECP2, KISS1, or KISS1R.
• TS14 patients exhibited lower median height and a higher incidence of being born small for gestational age (SGA).

Conclusions:

• Genetic and epigenetic causes were identified in 12.2% of the evaluated CPP patients.
• Suggests considering genetic testing for TS14 and MKRN3 defects in CPP patients born SGA or with a family history of paternal early puberty.