Yates, T.M., Vasudevan, P.C., Chandler, K.E. et al. (5 more authors) (2017) De novo mutations in HNRNPU result in a neurodevelopmental syndrome. American Journal of Medical Genetics Part A, 173 (11). pp. 3003-3012. ISSN 1552-4825
Abstract
Exome sequencing in the context of developmental disorders is a useful technique, but variants found need to be interpreted in the context of detailed phenotypic information. Whole gene deletions and loss-of-function-mutations in the HNRNPU gene have been associated with intellectual disability and seizures in some patients. However, a unifying syndromic phenotype has not been previously elucidated. Here, we report a total of seven patients (six patients identified through the Wellcome Trust Deciphering Developmental Disorders study, with one additional patient), who have heterozygous de novo mutations in HNRNPU. These were found via trio-based exome sequencing. All but one of the mutations is predicted to cause loss-of-function. These patients have dysmorphic features in common, including prominent eyebrows, long palpebral fissures, overhanging columella, and thin upper lip. All patients have developmental delay and intellectual disability (ID), ranging from moderate to severe. Seizures are common from early childhood. These initially occur in the context of febrile episodes. This series demonstrates common phenotypic features, including emerging dysmorphism, associated with heterozygous HNRNPU mutations. This allows us to define a novel neurodevelopmental syndrome, with a likely mechanism of haploinsufficiency.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Wiley Periodicals, Inc. This is an author produced version of a paper subsequently published in American Journal of Medical Genetics Part A. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Aggressive outbursts; behavior; HNRNPU; intellectual disability; seizures; trio exome sequencing |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Nov 2017 12:30 |
Last Modified: | 25 Sep 2018 00:38 |
Published Version: | https://doi.org/10.1002/ajmg.a.38492 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/ajmg.a.38492 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:124014 |