Discovery of a DNA methylation episignature as a molecular biomarker for fetal alcohol syndrome.

Liselot van der Laan; Raissa Relator; Irene Valenzuela; Adri N Mul; Mari&#xeb;lle Alders; Michael A Levy; Jennifer Kerkhof; Jessica Rzasa; Anna M Cueto-Gonz&#xe1;lez; Amaia Lasa-Aranzasti; Cristina Cea-Arestin; Marcel M A M Mannens; Mieke M van Haelst; Eduardo F Tizzano; Bekim Sadikovic; Peter Henneman

doi:10.1016/j.gim.2025.101586

PubMed · 40977504

Discovery of a DNA methylation episignature as a molecular biomarker for fetal alcohol syndrome.

Liselot van der Laan·Raissa Relator·Irene Valenzuela·Adri N Mul·Mariëlle Alders·Michael A Levy·Jennifer Kerkhof·Jessica Rzasa·Anna M Cueto-González·Amaia Lasa-Aranzasti·Cristina Cea-Arestin·Marcel M A M Mannens·Mieke M van Haelst·Eduardo F Tizzano·Bekim Sadikovic·Peter Henneman

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Abstract

PURPOSE: Fetal alcohol spectrum disorder (FASD) encompasses a range of clinical features and neurodevelopmental disorders in children exposed to alcohol in utero. Despite its global public health significance, FASD diagnosis remains challenging because of nonspecific clinical findings and the lack of an accurate molecular diagnostic biomarker. This study aimed to evaluate peripheral blood DNA methylation (DNAm) profiles as a potential diagnostic biomarker for fetal alcohol syndrome. METHODS: Genomic DNAm profiles from 93 individuals with suspected or confirmed FAS, including a clinically diagnosed FAS subgroup, were analyzed and compared with a large database of control and patient cohorts with previously reported DNAm episignatures. Functional analysis of these DNAm profiles was performed to identify episignatures and assess their potential diagnostic utility. RESULTS: A relatively sensitive and specific DNAm episignature for FAS was identified. Comparative epigenomic analysis revealed functional correlations between FAS and other rare genetic disorders, supporting the robustness of the identified DNAm profiles as a diagnostic tool. CONCLUSION: This study demonstrates that unique DNAm profiles provide a robust episignature biomarker for FAS. These findings contribute to the molecular understanding of FAS and hold promise for improving diagnostic accuracy for this complex disorder.

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Humans Fetal Alcohol Spectrum Disorders DNA Methylation Female Biomarkers Male Pregnancy Child Epigenomics Adult Epigenesis, Genetic DNA methylation Episignature FASD Fetal alcohol spectrum disorder Molecular biomarker Journal Article Research Support, Non-U.S. Gov't

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Liselot van der Laan, Raissa Relator, Irene Valenzuela, Adri N Mul, Mariëlle Alders, Michael A Levy, Jennifer Kerkhof, Jessica Rzasa, Anna M Cueto-González, Amaia Lasa-Aranzasti, Cristina Cea-Arestin, Marcel M A M Mannens, Mieke M van Haelst, Eduardo F Tizzano, Bekim Sadikovic, Peter Henneman. 2025-09-18. Discovery of a DNA methylation episignature as a molecular biomarker for fetal alcohol syndrome.. https://doi.org/10.1016/j.gim.2025.101586

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