biostudies-literatureFang XNational Center for Advancing Translational SciencesNICHD NIH HHSNCATS NIH HHSNational Institutes of HealthNIH HHSNational Institute of Child Health and Human Development160-173https://www.ebi.ac.uk/biostudies/studies/S-EPMC11911005biostudies-literatureUnknown194(2)Rett syndrome (RTT) is a progressive neurodevelopmental disorder, and pathogenic Methyl-CpG-binding Protein 2 (MECP2) variants are identified in >95% of individuals with typical RTT. Most of RTT-causing variants in MECP2 are de novo and usually on the paternally inherited X chromosome. While paternal age has been reported to be associated with increased risk of genetic disorders, it is unknown whether parental age contributes to the risk of the development of RTT. Clinical data including parental age, RTT diagnostic status, and clinical severity are collected from 1226 participants with RTT and confirmed MECP2 variants. Statistical analyses are performed using Student t-test, single factor analysis of variance (ANOVA), and multi-factor regression. No significant difference is observed in pAmerican journal of medical genetics. Part AParental age effects and Rett syndrome.PMC11911005P50 HD103537U54 HD061222Benke TAAnnese FEMarsh EDLane JBFang XPercy AKBaggett LMMotil KJCaylor RCNeul JLSkinner SAGlaze DGBarrish JOfalseParental age effects and Rett syndrome.Rett syndrome (RTT) is a progressive neurodevelopmental disorder, and pathogenic Methyl-CpG-binding Protein 2 (MECP2) variants are identified in >95% of individuals with typical RTT. Most of RTT-causing variants in MECP2 are de novo and usually on the paternally inherited X chromosome. While paternal age has been reported to be associated with increased risk of genetic disorders, it is unknown whether parental age contributes to the risk of the development of RTT. Clinical data including parental age, RTT diagnostic status, and clinical severity are collected from 1226 participants with RTT and confirmed MECP2 variants. Statistical analyses are performed using Student t-test, single factor analysis of variance (ANOVA), and multi-factor regression. No significant difference is observed in p2024-01-01T00:00:00Z2024 Feb2026-06-02T07:18:40.571Z2025-04-05T12:38:52.561ZS-EPMC119110053776818710.1002/ajmg.a.63396