Genome sequencing identifies major causes of severe intellectual disability
@article{Gilissen2014GenomeSI, title={Genome sequencing identifies major causes of severe intellectual disability}, author={Christian Gilissen and Jayne Y. Hehir-Kwa and D. T. Thung and Maartje van de Vorst and Bregje W.M. van Bon and Marjolein H Willemsen and Michael P. Kwint and Irene M. Janssen and Alexander Hoischen and Annette Schenck and Richard A Leach and Robert Klein and Rick Tearle and Tan Bo and Rolph Pfundt and Helger G Yntema and Bert B. A. de Vries and Tjitske Kleefstra and Han G. Brunner and Lisenka E.L.M. Vissers and Joris A. Veltman}, journal={Nature}, year={2014}, volume={511}, pages={344-347} }
Severe intellectual disability (ID) occurs in 0.5% of newborns and is thought to be largely genetic in origin. The extensive genetic heterogeneity of this disorder requires a genome-wide detection of all types of genetic variation. Microarray studies and, more recently, exome sequencing have demonstrated the importance of de novo copy number variations (CNVs) and single-nucleotide variations (SNVs) in ID, but the majority of cases remain undiagnosed. Here we applied whole-genome sequencing to…
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Genome-wide investigation of an ID cohort reveals de novo 3′UTR variants affecting gene expression
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The identification and characterization of de novo non-coding variation in 3′UTR regulatory regions within an ID cohort of 50 patients is described and two variants interfered with miRNA-mediated regulation of their target genes, AMD1 and FAIM.
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There were differences in the diagnostic yields of different variation types among the three ID subgroups, and the single-nucleotide variations showed a higher occurrence rate in the other IDs subgroup.
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The results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.
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- Biology, MedicineAmerican journal of medical genetics. Part A
- 2021
This is the first report of WGS analysis in Japanese patients with ID, and results would provide insight into the correlation between novel variants and expanded phenotypes of the disease.
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- Medicine, BiologyEuropean Journal of Human Genetics
- 2019
The causative role of variants in CXorf56 for an X-linked form of intellectual disability with additional neurological features is confirmed and the gene should be considered for molecular diagnostics of patients with ID, specifically when family history is suggestive of X- linked inheritance.
Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA.
- BiologyAmerican journal of human genetics
- 2016
High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing
- Medicine, BiologyJournal of Medical Genetics
- 2016
Next-generation sequencing has the potential for high-throughput identification of genetic variations, although the challenges of an adequate clinical interpretation of these variants and the knowledge on further unknown genes causing intellectual disability remain to be solved.
Targeted Next‐Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability
- Medicine, BiologyHuman mutation
- 2015
To diagnose patients with ID in the absence of parental DNA, it is recommended that investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes are investigated.
De Novo Mutations in Moderate or Severe Intellectual Disability
- Biology, MedicinePLoS genetics
- 2014
It is concluded that DNMs represent a major cause of moderate or severe ID.
Challenges in molecular diagnosis of X-linked Intellectual disability.
- Biology, MedicineBritish medical bulletin
- 2020
To improve variant interpretation, there is need to refine in silico predictions with specific criteria for each gene, and to develop cost-effective functional tools, which can be easily transferred to diagnostics.
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