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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It is concluded that DNMs represent a major cause of moderate or severe ID.
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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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