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使用全外显子组测序对自闭症谱系障碍和其他发育障碍儿童进行探索性遗传分析。

Exploratory genetic analysis in children with autism spectrum disorder and other developmental disorders using whole exome sequencing.

机构信息

Biocomputix, Sarajevo, Bosnia and Herzegovina; BioCertica, Paarl, South Africa.

International Burch University, Sarajevo, Bosnia and Herzegovina.

出版信息

Biomol Biomed. 2024 Feb 6;24(4):888-896. doi: 10.17305/bb.2024.10221.


DOI:10.17305/bb.2024.10221
PMID:38421723
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11293238/
Abstract

Developmental disorders (DDs), such as autism spectrum disorder (ASD), incorporate various conditions; once identified, further diagnostics are necessary to specify their type and severity. The aim of this exploratory study was to identify genetic variants that can help differentiate ASD early from other DDs. We selected 36 children (mean age 60.1 months) with DDs using Developmental Behavioral Scales (DBS) through "EDUS-Education for All", an organization providing services for children with developmental disorders in Bosnia and Herzegovina. We further rated children's autistic traits with the preschool version of the Childhood Autism Rating Scale, second edition (CARS-II). We defined ASD if scores were >25.5 and other DDs if scores were <25.5. Diagnosis of ASD and DD were independently confirmed by child psychiatrists. Whole exome sequencing (WES) was performed by Veritas Genetics, USA, using Illumina NovaSeq 6000 (Illumina Inc., San Diego, CA, USA) next-generation sequencing (NGS) apparatus. We tested genetic association by applying SKAT-O, which optimally combines the standard Sequence Kernel Association Test (SKAT) and burden tests to identify rare variants associated with complex traits in samples of limited power. The analysis yielded seven genes (DSE, COL10A1, DLK2, CSMD1, FAM47E, PPIA, PYDC2) to potentially differentiate observed phenotypic characteristics between our cohort participants with ASD and other DDs. Our exploratory study in a small sample of participants with ASD and other DDs contributed to gene discovery in differentiating ASD from DDs. A replication study is needed in a larger sample to confirm our results.

摘要

发育障碍(DDs),如自闭症谱系障碍(ASD),包含各种病症;一旦确定,需要进一步的诊断来确定其类型和严重程度。本探索性研究的目的是确定可以帮助早期区分 ASD 与其他 DDs 的遗传变异。我们通过“EDUS-全民教育”组织,使用发育行为量表(DBS)选择了 36 名患有 DDs 的儿童(平均年龄 60.1 个月),该组织为波斯尼亚和黑塞哥维那患有发育障碍的儿童提供服务。我们还使用儿童自闭症评定量表第二版(CARS-II)的学前版本对儿童的自闭症特征进行评分。如果评分>25.5,则定义为 ASD;如果评分<25.5,则定义为其他 DDs。ASD 和 DD 的诊断由儿童精神病学家独立确认。全外显子组测序(WES)由美国 Veritas Genetics 公司通过 Illumina NovaSeq 6000(Illumina Inc.,圣地亚哥,CA,USA)下一代测序(NGS)仪器进行。我们通过应用 SKAT-O 来测试遗传关联,该方法最佳地结合了标准序列核关联测试(SKAT)和负担测试,以在有限功率的样本中识别与复杂特征相关的罕见变异。该分析产生了七个基因(DSE、COL10A1、DLK2、CSMD1、FAM47E、PPIA、PYDC2),可能有助于区分我们的 ASD 队列参与者与其他 DDs 之间的观察到的表型特征。我们在 ASD 和其他 DDs 的小样本参与者中的探索性研究有助于发现区分 ASD 与 DDs 的基因。需要在更大的样本中进行复制研究来确认我们的结果。

相似文献

[1]
Exploratory genetic analysis in children with autism spectrum disorder and other developmental disorders using whole exome sequencing.

Biomol Biomed. 2024-2-6

[2]
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Orphanet J Rare Dis. 2024-5-19

[3]
Whole Exome Sequencing Identifies Novel De Novo Variants Interacting with Six Gene Networks in Autism Spectrum Disorder.

Genes (Basel). 2020-12-22

[4]
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[5]
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Genes (Basel). 2021-12-23

[6]
Autism spectrum disorder and birth spacing: Findings from the study to explore early development (SEED).

Autism Res. 2017-11-22

[7]
Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test.

Genes (Basel). 2021-4-12

[8]
Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 4 Years - Early Autism and Developmental Disabilities Monitoring Network, Seven Sites, United States, 2010, 2012, and 2014.

MMWR Surveill Summ. 2019-4-12

[9]
Identification of Developmental and Behavioral Markers Associated With Genetic Abnormalities in Autism Spectrum Disorder.

Am J Psychiatry. 2017-6-1

[10]
Comparative yield of molecular diagnostic algorithms for autism spectrum disorder diagnosis in India: evidence supporting whole exome sequencing as first tier test.

BMC Neurol. 2023-8-5

本文引用的文献

[1]
Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020.

MMWR Surveill Summ. 2023-3-24

[2]
Practice Patterns and Potential Barriers to Early Diagnosis of Autism in Bosnia and Herzegovina: A Preliminary Study.

J Autism Dev Disord. 2021-12

[3]
The uncharacterized protein FAM47E interacts with PRMT5 and regulates its functions.

Life Sci Alliance. 2021-3

[4]
The Relationship between Autism and Ehlers-Danlos Syndromes/Hypermobility Spectrum Disorders.

J Pers Med. 2020-12-1

[5]
Differences in Body Mass Index (BMI) in Early Adolescents with Autism Spectrum Disorder Compared to Youth with Typical Development.

J Autism Dev Disord. 2021-8

[6]
The risk of overweight and obesity in children with autism spectrum disorders: A systematic review and meta-analysis.

Obes Rev. 2019-10-8

[7]
Improving the diagnostic yield of exome- sequencing by predicting gene-phenotype associations using large-scale gene expression analysis.

Nat Commun. 2019-6-28

[8]
Association between schizophrenia and autism spectrum disorder: A systematic review and meta-analysis.

Autism Res. 2018-10-3

[9]
Autism spectrum disorder: advances in diagnosis and evaluation.

BMJ. 2018-5-21

[10]
Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014.

MMWR Surveill Summ. 2018-4-27

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