Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder.
Autor: | Regev O; Joyce & Irving Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.; Department of Epidemiology, Biostatistics and Community Health Sciences, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Shil A; Department of Epidemiology, Biostatistics and Community Health Sciences, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Bronshtein T; Joyce & Irving Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Hadar A; Clalit Health Services, Beer-Sheva, Israel.; Division of Obstetrics and Gynecology, Soroka University Medical Center, Beer-Sheva, Israel., Meiri G; Preschool Psychiatric Unit, Soroka University Medical Center, Beer-Sheva, Israel.; Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Zigdon D; Preschool Psychiatric Unit, Soroka University Medical Center, Beer-Sheva, Israel.; Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Michaelovski A; Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer-Sheva, Israel.; Child Development Center, Soroka University Medical Center, Beer-Sheva, Israel., Hershkovitz R; Division of Obstetrics and Gynecology, Soroka University Medical Center, Beer-Sheva, Israel., Menashe I; Department of Epidemiology, Biostatistics and Community Health Sciences, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. idanmen@bgu.ac.il.; Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer-Sheva, Israel. idanmen@bgu.ac.il. |
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Jazyk: | angličtina |
Zdroj: | Journal of neurodevelopmental disorders [J Neurodev Disord] 2024 Sep 30; Vol. 16 (1), pp. 55. Date of Electronic Publication: 2024 Sep 30. |
DOI: | 10.1186/s11689-024-09573-6 |
Abstrakt: | Background: Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings are associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. Methods: The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline, AutScore, to these WES data to prioritize rare, gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. Results: The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR = 2.55, 95%CI: 1.13-5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR = 8.28, 95%CI: 2.29-30.01; LoF: aOR = 5.72, 95%CI: 2.08-15.71 and any mutation: aOR = 6.39, 95%CI: 1.34-30.47; LoF: aOR = 4.50, 95%CI: 1.32-15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR = 2.76, 95%CI: 1.14-6.68). There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21, P = 0.016). Conclusions: The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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