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分离扩展自闭症谱系障碍(ASD)家系中拷贝数变异的分离模式。

Segregating patterns of copy number variations in extended autism spectrum disorder (ASD) pedigrees.

机构信息

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.

出版信息

Am J Med Genet B Neuropsychiatr Genet. 2020 Jul;183(5):268-276. doi: 10.1002/ajmg.b.32785. Epub 2020 May 6.


DOI:10.1002/ajmg.b.32785
PMID:32372567
Abstract

Autism spectrum disorder (ASD) is a relatively common childhood onset neurodevelopmental disorder with a complex genetic etiology. While progress has been made in identifying the de novo mutational landscape of ASD, the genetic factors that underpin the ASD's tendency to run in families are not well understood. In this study, nine extended pedigrees each with three or more individuals with ASD, and others with a lesser autism phenotype, were phenotyped and genotyped in an attempt to identify heritable copy number variants (CNVs). Although these families have previously generated linkage signals, no rare CNV segregated with these signals in any family. A small number of clinically relevant CNVs were identified. Only one CNV was identified that segregated with ASD phenotype; namely, a duplication overlapping DLGAP2 in three male offspring each with an ASD diagnosis. This gene encodes a synaptic scaffolding protein, part of a group of proteins known to be pathologically implicated in ASD. On the whole, however, the heritable nature of ASD in the families studied remains poorly understood.

摘要

自闭症谱系障碍(ASD)是一种较为常见的儿童期起病的神经发育障碍,具有复杂的遗传病因。虽然在识别 ASD 的新生突变景观方面已经取得了进展,但自闭症谱系障碍在家族中倾向于遗传的遗传因素尚不清楚。在这项研究中,对 9 个扩展的家系进行了表型和基因型分析,每个家系有 3 个或更多的 ASD 患者和其他具有较轻自闭症表型的个体,试图识别可遗传的拷贝数变异(CNVs)。尽管这些家系先前已经产生了连锁信号,但在任何一个家系中,都没有罕见的 CNV 与这些信号分离。确定了少数具有临床意义的 CNVs。只有一个 CNV 与 ASD 表型分离;即,在三个男性后代中重叠 DLGAP2 的重复,每个后代都被诊断为 ASD。该基因编码一种突触支架蛋白,是一组已知与 ASD 病理相关的蛋白。然而,总的来说,在所研究的家系中,自闭症谱系障碍的可遗传性仍知之甚少。

相似文献

[1]
Segregating patterns of copy number variations in extended autism spectrum disorder (ASD) pedigrees.

Am J Med Genet B Neuropsychiatr Genet. 2020-7

[2]
Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank.

Mol Autism. 2021-2-10

[3]
A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees.

J Neurodev Disord. 2018-6-11

[4]
Using extended pedigrees to identify novel autism spectrum disorder (ASD) candidate genes.

Hum Genet. 2014-11-29

[5]
Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder.

Mol Autism. 2016-4-1

[6]
Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.

Nat Commun. 2019-12-5

[7]
Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families.

Am J Hum Genet. 2016-9-1

[8]
An integrated analysis of rare CNV and exome variation in Autism Spectrum Disorder using the Infinium PsychArray.

Sci Rep. 2020-2-21

[9]
High resolution analysis of rare copy number variants in patients with autism spectrum disorder from Taiwan.

Sci Rep. 2017-9-20

[10]
Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders.

J Neurodev Disord. 2019-2-7

引用本文的文献

[1]
Chromosome X-wide common variant association study in autism spectrum disorder.

Am J Hum Genet. 2025-1-2

[2]
Chromosome X-Wide Common Variant Association Study (XWAS) in Autism Spectrum Disorder.

medRxiv. 2024-7-18

[3]
The Phenotypic variability of 16p11.2 distal BP2-BP3 deletion in a transgenerational family and in neurodevelopmentally ascertained samples.

J Med Genet. 2023-11-27

[4]
Gene copy number variation and pediatric mental health/neurodevelopment in a general population.

Hum Mol Genet. 2023-7-20

[5]
SAPAP Scaffold Proteins: From Synaptic Function to Neuropsychiatric Disorders.

Cells. 2022-11-28

[6]
Diagnostic Yield and Economic Implications of Whole-Exome Sequencing for ASD Diagnosis in Israel.

Genes (Basel). 2021-12-23

[7]
8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature.

Genes (Basel). 2021-4-27

[8]
The Emerging Physiological Role of AGMO 10 Years after Its Gene Identification.

Life (Basel). 2021-1-26

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