在 135 名患者中，基于杂交的 17 个 X 连锁智力障碍基因重测序揭示了 ATRX、SLC6A8 和 PQBP1 中的新突变。
Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1.
机构信息
Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
出版信息
Eur J Hum Genet. 2011 Jun;19(6):717-20. doi: 10.1038/ejhg.2010.244. Epub 2011 Jan 26.
Abstract
X-linked intellectual disability (XLID), also known as X-linked mental retardation, is a highly genetically heterogeneous condition for which mutations in >90 different genes have been identified. In this study, we used a custom-made sequencing array based on the Affymetrix 50k platform for mutation screening in 17 known XLID genes in patients from 135 families and found eight single-nucleotide changes that were absent in controls. For four mutations affecting ATRX (p.1761M>T), PQBP1 (p.155R>X) and SLC6A8 (p.390P>L and p.477S>L), we provide evidence for a functional involvement of these changes in the aetiology of intellectual disability.
摘要
X 连锁智力障碍（XLID），也称为 X 连锁智力迟钝，是一种高度遗传异质性的疾病，已经确定了 >90 种不同基因的突变。在这项研究中，我们使用了基于 Affymetrix 50k 平台的定制测序芯片，对来自 135 个家系的 17 个已知 XLID 基因的患者进行了突变筛选，发现了 8 个在对照组中不存在的单核苷酸变化。对于影响 ATRX（p.1761M>T）、PQBP1（p.155R>X）和 SLC6A8（p.390P>L 和 p.477S>L）的四个突变，我们提供了这些变化在智力障碍发病机制中具有功能相关性的证据。
相似文献
1
Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1.
Eur J Hum Genet. 2011 Jun;19(6):717-20. doi: 10.1038/ejhg.2010.244. Epub 2011 Jan 26.
2
Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability.
Genes (Basel). 2020 Jan 2;11(1):51. doi: 10.3390/genes11010051.
3
Novel ATRX gene damaging missense mutation c.6740A>C segregates with profound to severe intellectual deficiency without alpha thalassaemia.
Indian J Med Res. 2016 Jan;143(1):43-8. doi: 10.4103/0971-5916.178589.
4
Duplication at Xq13.3-q21.1 with syndromic intellectual disability, a probable role for the ATRX gene.
Am J Med Genet A. 2014 Apr;164A(4):918-23. doi: 10.1002/ajmg.a.36371. Epub 2014 Jan 23.
5
Detection of a novel intragenic rearrangement in the creatine transporter gene by next generation sequencing.
Mol Genet Metab. 2013 Dec;110(4):465-71. doi: 10.1016/j.ymgme.2013.09.018. Epub 2013 Oct 4.
6
Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes.
Hum Mutat. 2014 Jan;35(1):58-62. doi: 10.1002/humu.22465.
7
Phenotype and genotype in 101 males with X-linked creatine transporter deficiency.
J Med Genet. 2013 Jul;50(7):463-72. doi: 10.1136/jmedgenet-2013-101658. Epub 2013 May 3.
8
High prevalence of SLC6A8 deficiency in X-linked mental retardation.
Am J Hum Genet. 2004 Jul;75(1):97-105. doi: 10.1086/422102. Epub 2004 May 20.
9
The screening of SLC6A8 deficiency among Estonian families with X-linked mental retardation.
J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S5-11. doi: 10.1007/s10545-008-1063-y.
10
Inherited germline ATRX mutation in two brothers with ATR-X syndrome and osteosarcoma.
Am J Med Genet A. 2017 May;173(5):1390-1395. doi: 10.1002/ajmg.a.38184. Epub 2017 Mar 28.
引用本文的文献
1
Molecular consequences of PQBP1 deficiency, involved in the X-linked Renpenning syndrome.
Mol Psychiatry. 2024 Feb;29(2):287-296. doi: 10.1038/s41380-023-02323-5. Epub 2023 Nov 29.
2
A rigorous genomic interrogation at 1p13.3 reveals 16 autosomal dominant candidate genes in syndromic neurodevelopmental disorders.
Front Mol Neurosci. 2022 Oct 6;15:979061. doi: 10.3389/fnmol.2022.979061. eCollection 2022.
3
X-linked mental retardation-hypotonic facies syndrome: Exome sequencing identifies novel clinical characteristics associated with c.5182G>C mutation in the ATRX gene.
Mol Genet Genomic Med. 2022 Oct;10(10):e2034. doi: 10.1002/mgg3.2034. Epub 2022 Aug 13.
4
PQBP1: The Key to Intellectual Disability, Neurodegenerative Diseases, and Innate Immunity.
Int J Mol Sci. 2022 Jun 2;23(11):6227. doi: 10.3390/ijms23116227.
5
Brief Report: Evidence of Autism Spectrum Disorder Caused by a Mutation in ATRX Gene: A Case Report.
J Autism Dev Disord. 2024 Jan;54(1):379-388. doi: 10.1007/s10803-022-05588-x. Epub 2022 May 20.
6
Mapping the landscape of tandem repeat variability by targeted long read single molecule sequencing in familial X-linked intellectual disability.
BMC Med Genomics. 2018 Dec 19;11(1):123. doi: 10.1186/s12920-018-0446-7.
7
Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome.
Sci Rep. 2016 Jul 26;6:30293. doi: 10.1038/srep30293.
8
Novel ATRX gene damaging missense mutation c.6740A>C segregates with profound to severe intellectual deficiency without alpha thalassaemia.
Indian J Med Res. 2016 Jan;143(1):43-8. doi: 10.4103/0971-5916.178589.
9
Development of a high-throughput resequencing array for the detection of pathogenic mutations in osteogenesis imperfecta.
PLoS One. 2015 Mar 5;10(3):e0119553. doi: 10.1371/journal.pone.0119553. eCollection 2015.
10
Prioritizing genes for X-linked diseases using population exome data.
Hum Mol Genet. 2015 Feb 1;24(3):599-608. doi: 10.1093/hmg/ddu473. Epub 2014 Sep 12.
本文引用的文献
1
High-throughput resequencing in the diagnosis of BRCA1/2 mutations using oligonucleotide resequencing microarrays.
Breast Cancer Res Treat. 2010 Jul;122(1):287-97. doi: 10.1007/s10549-009-0639-z. Epub 2009 Nov 26.
2
Common pathological mutations in PQBP1 induce nonsense-mediated mRNA decay and enhance exclusion of the mutant exon.
Hum Mutat. 2010 Jan;31(1):90-8. doi: 10.1002/humu.21146.
3
The genetic landscape of intellectual disability arising from chromosome X.
Trends Genet. 2009 Jul;25(7):308-16. doi: 10.1016/j.tig.2009.05.002. Epub 2009 Jun 24.
4
Hybrid selection of discrete genomic intervals on custom-designed microarrays for massively parallel sequencing.
Nat Protoc. 2009;4(6):960-74. doi: 10.1038/nprot.2009.68. Epub 2009 May 28.
5
A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation.
Nat Genet. 2009 May;41(5):535-43. doi: 10.1038/ng.367. Epub 2009 Apr 19.
6
An overview of custom array sequencing.
Curr Protoc Hum Genet. 2009 Apr;Chapter 7:Unit 7.17. doi: 10.1002/0471142905.hg0717s61.
7
Genetics of intellectual disability.
Curr Opin Genet Dev. 2008 Jun;18(3):241-50. doi: 10.1016/j.gde.2008.07.008. Epub 2008 Aug 28.
8
Validation of microarray-based resequencing of 93 worldwide mitochondrial genomes.
Hum Mutat. 2009 Jan;30(1):115-22. doi: 10.1002/humu.20816.
9
A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy.
Hum Mutat. 2008 Jun;29(6):879-85. doi: 10.1002/humu.20749.
10
Functional characterization of missense variants in the creatine transporter gene (SLC6A8): improved diagnostic application.
Hum Mutat. 2007 Sep;28(9):890-6. doi: 10.1002/humu.20532.
Zotero 插件