Journal article

Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability

David Hunt, Richard J Leventer, Cas Simons, Ryan Taft, Kathryn J Swoboda, Mary Gawne-Cain, Alex C Magee, Peter D Turnpenny, Diana Baralle



BACKGROUND: De novo mutations are emerging as an important cause of neurocognitive impairment, and whole exome sequencing of case-parent trios is a powerful way of detecting them. Here, we report the findings in four such trios. METHODS: The Deciphering Developmental Disorders study is using whole exome sequencing in family trios to investigate children with severe, sporadic, undiagnosed developmental delay. Three of our patients were ascertained from the first 1133 children to have been investigated through this large-scale study. Case 4 was a phenotypically isolated case recruited into an undiagnosed rare disorders sequencing study. RESULTS: Protein-altering de novo mutations in PURA were ..

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Awarded by Health Innovation Challenge Fund

Awarded by Wellcome Trust Sanger Institute

Funding Acknowledgements

The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of the Wellcome Trust or the Department of Health. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. We would like to thank Associate Professor Avihu Boneh and Dr Diana Johnston who contributed clinical data for Patient 4. We thank the patients and their families for their participation. DB is a Hefce senior clinical fellow.