Exonic deletions of <i>AUTS2</i> in Chinese patients with developmental delay and intellectual disability

Fan, Yanjie; Qiu, Wenjuan; Wang, Lili; Gu, Xuefan; Yu, Yongguo

doi:10.1002/ajmg.a.37454

Cited by 14 publications

(15 citation statements)

References 15 publications

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“…Auts2 (Autism Susceptibility Candidate 2) is an ASD candidate gene that has been associated with ASD and other neurodevelopmental disorders that are comorbid with ASD, including intellectual disability 62 and developmental delay 62 . Auts2 is abundantly expressed in the developing brain and is mostly expressed in the hippocampus, prefrontal cortex, and cerebellum 63 , which are brain regions known to be impacted in individuals with ASD 64 .…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus

Thongkorn

Kanlayaprasit

Jindatip

et al. 2019

Sci Rep

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder inexplicably biased towards males. Although prenatal exposure to bisphenol A (BPA) has recently been associated with the ASD risk, whether BPA dysregulates ASD-related genes in the developing brain remains unclear. In this study, transcriptome profiling by RNA-seq analysis of hippocampi isolated from neonatal pups prenatally exposed to BPA was conducted and revealed a list of differentially expressed genes (DEGs) associated with ASD. Among the DEGs, several ASD candidate genes, including Auts2 and Foxp2 , were dysregulated and showed sex differences in response to BPA exposure. The interactome and pathway analyses of DEGs using Ingenuity Pathway Analysis software revealed significant associations between the DEGs in males and neurological functions/disorders associated with ASD. Moreover, the reanalysis of transcriptome profiling data from previously published BPA studies consistently showed that BPA-responsive genes were significantly associated with ASD-related genes. The findings from this study indicate that prenatal BPA exposure alters the expression of ASD-linked genes in the hippocampus and suggest that maternal BPA exposure may increase ASD susceptibility by dysregulating genes associated with neurological functions known to be negatively impacted in ASD, which deserves further investigations.

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Section: Discussionmentioning

confidence: 99%

Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus

Thongkorn

Kanlayaprasit

Jindatip

et al. 2019

Sci Rep

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“…Typically de novo intragenic deletions, varying in size (from 4 kb to 4.1 Mb) and affecting different exons and/or introns of the AUTS2 gene, have been described in patients with intellectual and developmental delay, which could also include other features such as microcephaly, short stature, feeding problems, hypotonia, or recurrent dysmorphic features (Amarillo, Li, Li, Vilain, & Kantarci, 2014; Beunders et al, 2013; Beunders et al, 2016; Fan, Qiu, Wang, Gu, & Yu, 2016; Jolley et al, 2013; Nagamani et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

De novo small deletion affecting transcription start site of short isoform of AUTS2 gene in a patient with syndromic neurodevelopmental defects

Martı́nez-Delgado

López-Martín

Lara-Herguedas

et al. 2020

American J of Med Genetics Pt A

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Disruption of the autism susceptibility candidate 2 (AUTS2) gene through genomic rearrangements, copy number variations (CNVs), and intragenic deletions and mutations, has been recurrently involved in syndromic forms of developmental delay and intellectual disability, known as AUTS2 syndrome. The AUTS2 gene plays an important role in regulation of neuronal migration, and when altered, associates with a variable phenotype from severely to mildly affected patients. The more severe phenotypes significantly correlate with the presence of defects affecting the C‐terminus part of the gene. This article reports a new patient with a syndromic neurodevelopmental disorder, who presents a deletion of 30 nucleotides in the exon 9 of the AUTS2 gene. Importantly, this deletion includes the transcription start site for the AUTS2 short transcript isoform, which has an important role in brain development. Gene expression analysis of AUTS2 full‐length and short isoforms revealed that the deletion found in this patient causes a remarkable reduction in the expression level, not only of the short isoform, but also of the full AUTS2 transcripts. This report adds more evidence for the role of mutated AUTS2 short transcripts in the development of a severe phenotype in the AUTS2 syndrome.

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“…For undiagnosed patient by NGS in this study, CMA was performed using Affymetrix CytoScan HD array as previously described [16]. The pathogenicity of detected CNVs and loss of heterozygocity regions (LOH) were classified based on the ACMG recommendations [17].…”

Section: Cma and Validationmentioning

confidence: 99%

Genetic Evaluation of 114 Chinese Short Stature Children in the Next Generation Era: a Single Center Study

Huang

Sun

Fan

et al. 2018

Cell Physiol Biochem

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Background/Aims: The genetics of human height is a frequently studied and complex issue. However, there is limited genetic research of short stature. To uncover the subgroup of patients to have higher yield and to propose a simplified diagnostic algorithm in the next generation era. Methods: This study included 114 Chinese children with height SDS ≤ -2.5 and unknown etiology from 2014 to 2015. Target/whole exome sequencing (referred as NGS) and chromosomal microarray analysis (CMA) were performed on the enrolled patients sequentially to identify potential genetic etiologies. The samples solved by NGS and CMA were retrospectively studied to evaluate the clinical pathway of the patients following a standard diagnostic algorithm. Results: In total, a potential genetic etiology was identified in 41 (36%) patients: 38 by NGS (33.3%), two by CMA (1.8%), and an additional one by both (0.9%). There were 46 different variants in 29 genes and 2 pathogenic CNVs identified. The diagnostic yield was significantly higher in patients with facial dysmorphism or skeletal abnormalities than those without the corresponding phenotype (P=0.006 and P=0.009, respectively, Pearson’s χ² test). Retrospectively study the cohort indicate 83.3% patients eventually would be evaluated by NGS/CMA. Conclusion: This study confirms the utility of high-throughput molecular detection techniques for the etiological diagnosis of undiagnosed short stature and suggests that NGS could be used as a primary diagnostic strategy. Patients with facial dysmorphism and/or skeletal abnormalities are more likely to have a known genetic etiology. Moving NGS forward would simplified the diagnostic algorithm.

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Exonic deletions of AUTS2 in Chinese patients with developmental delay and intellectual disability

Cited by 14 publications

References 15 publications

Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus

Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus

De novo small deletion affecting transcription start site of short isoform of AUTS2 gene in a patient with syndromic neurodevelopmental defects

Genetic Evaluation of 114 Chinese Short Stature Children in the Next Generation Era: a Single Center Study

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