Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder

被引:1
作者
Regev, Ohad [1 ,2 ]
Shil, Apurba [2 ]
Bronshtein, Tal [1 ]
Hadar, Amnon [3 ,4 ]
Meiri, Gal [5 ,6 ]
Zigdon, Dikla [5 ,6 ]
Michaelovski, Analya [6 ,7 ]
Hershkovitz, Reli [4 ]
Menashe, Idan [2 ,6 ]
机构
[1] Ben Gurion Univ Negev, Fac Hlth Sci, Joyce & Irving Goldman Med Sch, Beer Sheva, Israel
[2] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol Biostat & Community Hlth Sci, Beer Sheva, Israel
[3] Clalit Hlth Serv, Beer Sheva, Israel
[4] Soroka Univ, Med Ctr, Div Obstet & Gynecol, Beer Sheva, Israel
[5] Soroka Univ, Med Ctr, Presch Psychiat Unit, Beer Sheva, Israel
[6] Ben Gurion Univ Negev, Azrieli Natl Ctr Autism & Neurodev Res, Beer Sheva, Israel
[7] Soroka Univ, Child Dev Ctr, Med Ctr, Beer Sheva, Israel
基金
以色列科学基金会;
关键词
Autism spectrum disorder; Prenatal ultrasound; Fetal development; Whole-exome sequencing; Congenital anomalies; Ultrasonography fetal anomalies; Genetic mutations; DE-NOVO MUTATIONS; PRENATAL-DIAGNOSIS; DELETION SYNDROME; HEAD GROWTH; ABNORMALITIES; PHENOTYPE; DISEASE; ROUTINE; RISK; ASD;
D O I
10.1186/s11689-024-09573-6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
BackgroundRecent 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.MethodsThe 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.ResultsThe 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).ConclusionsThe 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.
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页数:12
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