DNA methylation differences in monozygotic twins with Van der Woude syndrome

• DOI: 10.3389/fdmed.2023.1120948
• Publication Date: 2023-02-17T09:11:31Z
• Authors: A. L. Petrin; E. Zeng; M. A. Thomas; D. Moretti-Ferreira; M. L. Marazita; X. J. Xie; J. C. Murray; L. M. Moreno-Uribe
• Keywords: cleft palate; 0301 basic medicine; DNA methylation; phenotypic discordance; epigenetics (DNA methylation); RK1-715; cleft lip; Article; 3. Good health; 03 medical and health sciences; monozygotic twins; Dentistry; lip pits; Van der Woude syndrome; Van der Woude

Introduction Van der Woude syndrome (VWS) is an autosomal dominant disorder responsible for 2% of all syndromic orofacial clefts (OFCs), with IRF6 being the primary causal gene (70%). Cases may present lip pits and either cleft lip, palate, or marked phenotypic discordance even among individuals carrying same mutation. This suggests that genetic epigenetic modifiers play additional roles in syndrome's etiology variability expression. We report first DNA methylation profiling two pairs monozygotic twins VWS. Our goal to explore contributions VWS variable expressivity by comparing DNAm profiles both twin pairs. While mutations cause these are known, mechanism behind their risk expression remains unclear. Methods generated whole genome data Differentially methylated positions (DMPs) were selected based on: (1) a coefficient variation levels unaffected <20%, (2) intra-twin pair absolute difference >5% (Δ β > |0.05|). then divided DMPs into subgroups each further analysis: higher A (Twin Twin B); B >Twin A). Results Discussion Gene ontology analysis revealed list enriched genes showed significant differential DNAm, including clef-associated genes. Among cleft-associated genes, TP63 was most hit (p = 7.82E-12). Both presented CpG sites in/near 1A 1B 2A < 2B). The function biological regulatory loop coordinate epithelial proliferation differentiation process critical palatal fusion. effects can be impacted dysregulation itself its pathway. show evidence changes plausible lead markedly distinct phenotypes,