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  • DNA Methylation Signature f...
    Verberne, Eline A.; van der Laan, Liselot; Haghshenas, Sadegheh; Rooney, Kathleen; Levy, Michael A.; Alders, Mariëlle; Maas, Saskia M.; Jansen, Sandra; Lieden, Agne; Anderlid, Britt-Marie; Rafael-Croes, Louise; Campeau, Philippe M.; Chaudhry, Ayeshah; Koolen, David A.; Pfundt, Rolph; Hurst, Anna C. E.; Tran-Mau-Them, Frederic; Bruel, Ange-Line; Lambert, Laetitia; Isidor, Bertrand; Mannens, Marcel M. A. M.; Sadikovic, Bekim; Henneman, Peter; van Haelst, Mieke M.

    International journal of molecular sciences, 07/2022, Letnik: 23, Številka: 14
    Journal Article

    JARID2 (Jumonji, AT Rich Interactive Domain 2) pathogenic variants cause a neurodevelopmental syndrome, that is characterized by developmental delay, cognitive impairment, hypotonia, autistic features, behavior abnormalities and dysmorphic facial features. JARID2 encodes a transcriptional repressor protein that regulates the activity of various histone methyltransferase complexes. However, the molecular etiology is not fully understood, and JARID2-neurodevelopmental syndrome may vary in its typical clinical phenotype. In addition, the detection of variants of uncertain significance (VUSs) often results in a delay of final diagnosis which could hamper the appropriate care. In this study we aim to detect a specific and sensitive DNA methylation signature for JARID2-neurodevelopmental syndrome. Peripheral blood DNA methylation profiles from 56 control subjects, 8 patients with (likely) pathogenic JARID2 variants and 3 patients with JARID2 VUSs were analyzed. DNA methylation analysis indicated a clear and robust separation between patients with (likely) pathogenic variants and controls. A binary model capable of classifying patients with the JARID2-neurodevelopmental syndrome was constructed on the basis of the identified episignature. Patients carrying VUSs clustered with the control group. We identified a distinct DNA methylation signature associated with JARID2-neurodevelopmental syndrome, establishing its utility as a biomarker for this syndrome and expanding the EpiSign diagnostic test.