2026-06-08T23:32:06Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1307252026-01-22T01:02:06Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Breen, Michael S. author Moreno Ruiz, María del Carmen author Parellada Redondo, María José author De Rubeis, Silvia author 2020-09-03 Helsmoortel-Van der Aa syndrome (HVDAS) is a neurodevelopmental condition associated with intellectual disability/developmental delay, autism spectrum disorder, and multiple medical comorbidities. HVDAS is caused by mutations in activity-dependent neuroprotective protein (ADNP). A recent study identified genome-wide DNA methylation changes in 22 individuals with HVDAS, adding to the group of neurodevelopmental disorders with an epigenetic signature. This methylation signature segregated those with HVDAS into two groups based on the location of the mutations. Here, we conducted an independent study on 24 individuals with HVDAS and replicated the existence of the two mutation-dependent episignatures. To probe whether the two distinct episignatures correlate with clinical outcomes, we used deep behavioral and neurobiological data from two prospective cohorts of individuals with a genetic diagnosis of HVDAS. We found limited phenotypic differences between the two HVDAS-affected groups and no evidence that individuals with more widespread methylation changes are more severely affected. Moreover, in spite of the methylation changes, we observed no profound alterations in the blood transcriptome of individuals with HVDAS. Our data warrant caution in harnessing methylation signatures in HVDAS as a tool for clinical stratification, at least with regard to behavioral phenotypes. Breen, M. S., Garg, P., Tang, L., Mendonca, D., Levy, T., Barbosa, M., Arnett, A. B., Kurtz-Nelson, E., Agolini, E., Battaglia, A., Chiocchetti, A. G., Freitag, C. M., Garcia-Alcon, A., Grammatico, P., Hertz-Picciotto, I., Ludena-Rodriguez, Y., Moreno, C., Novelli, A., Parellada, M., Pascolini, G., … De Rubeis, S. (2020). Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype. American journal of human genetics, 107(3), 555–563. https://doi.org/10.1016/j.ajhg.2020.07.003 0002-9297 10.1016/j.ajhg.2020.07.003 https://hdl.handle.net/20.500.14352/130725 1537-6605 https://doi.org/10.1016/j.ajhg.2020.07.003 https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(20)30233-0 https://pubmed.ncbi.nlm.nih.gov/32758449/ Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype