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De Novo Coding Variants Are Strongly Associated with Tourette Disorder.
- Source :
-
Neuron . May2017, Vol. 94 Issue 3, p486-499.e9. 1p. - Publication Year :
- 2017
-
Abstract
- Summary Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. Video Abstract [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08966273
- Volume :
- 94
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 122826147
- Full Text :
- https://doi.org/10.1016/j.neuron.2017.04.024