DNA methylation signature and clinical delineation of PACS1-related disorder in 24 unreported individuals - PubMed
5 hours ago
- #Epigenetics
- #DNA Methylation
- #Neurodevelopmental Disorder
- This study describes the clinical and DNA methylation analysis of 24 previously unreported individuals with PACS1-related disorder (PACS1-RD), also known as Schuurs-Hoeijmakers syndrome.
- It expands the known phenotypic spectrum, reporting median ages for independent walking and first words (both 24 months), and high prevalence of features like feeding difficulties (75%), cryptorchidism (77.8%), congenital heart defects (45.8%), and hypotonia (75%).
- Newly described clinical features include congenital kidney malformations (25%).
- Genome-wide DNA methylation profiling identified a specific epigenetic signature (episignature) for PACS1-RD, present in individuals with both the common p.(Arg203Trp) variant and a non-recurrent p.(Arg203Gln) variant.
- This DNA methylation episignature aided in diagnosing a case initially suspected of Kabuki syndrome, demonstrating its utility for diagnostic support and pathogenicity assessment of variants.