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Clinical findings of 21 previously unreported probands with HNRNPU-related syndrome and comprehensive literature review

Clinical findings of 21 previously unreported probands with HNRNPU-related syndrome and comprehensive literature review
Clinical findings of 21 previously unreported probands with HNRNPU-related syndrome and comprehensive literature review
With advances in genetic testing and improved access to such advances, whole exome sequencing is becoming a first line investigation in clinical work-up of children with developmental delay/ intellectual disability. As a result, the need to understand the importance of genetic variants and its effect on the clinical phenotype is increasing.

Here we report on the largest cohort of patients with HNRNPU variants. These twenty one patients follow on from the previous study published by Yates et al., 2017 from our group predominantly identified from the Deciphering Developmental Disorders (DDD) study that reported seven patients with HNRNPU variants. All the probands reported here have a de novo loss-of-function variant.

These probands have craniofacial dysmorphic features, in the majority including widely spaced teeth, microcephaly, high arched eyebrows and palpebral fissure abnormalities. Many of the patients in the group also have moderate-severe intellectual disability and seizures that tend to start in early childhood.

This series has allowed us to define a novel neurodevelopmental syndrome, with a likely mechanism of haploinsufficiency, and expand substantially on already published literature on HNRNPU-related neurodevelopmental syndrome.
DDD study, HNRNPU, exome sequencing, intellectual disability, seizures
1552-4825
1637-1654
Durkin, A
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Albaba, S
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Fry, AE
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Morton, Jenny E
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Douglas, Andrew
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Beleza, A
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Williams, D
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Volker-Touw, CML
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Lynch, S. A.
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Canham, N.
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Clowes, V.
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Straub, V.
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Lachlan, Katherine
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Gibbon, Frances
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El Gamal, M
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Verghese, V
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Parker, M. J.
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Newbury-Ecob, Ruth
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Turnpenny, Peter D.
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Gardham, A
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Ghali, N.
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Balasubramanian, M.
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DDD Study
Durkin, A
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Albaba, S
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Fry, AE
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Morton, Jenny E
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Douglas, Andrew
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Beleza, A
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Williams, D
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Volker-Touw, CML
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Lynch, S. A.
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Canham, N.
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Clowes, V.
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Straub, V.
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Lachlan, Katherine
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Gibbon, Frances
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El Gamal, M
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Verghese, V
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Parker, M. J.
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Newbury-Ecob, Ruth
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Turnpenny, Peter D.
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Gardham, A
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Ghali, N.
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Balasubramanian, M.
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Durkin, A, Albaba, S, Fry, AE, Morton, Jenny E, Douglas, Andrew, Beleza, A, Williams, D, Volker-Touw, CML, Lynch, S. A., Canham, N., Clowes, V., Straub, V., Lachlan, Katherine, Gibbon, Frances, El Gamal, M, Verghese, V, Parker, M. J., Newbury-Ecob, Ruth, Turnpenny, Peter D., Gardham, A, Ghali, N. and Balasubramanian, M. , DDD Study (2021) Clinical findings of 21 previously unreported probands with HNRNPU-related syndrome and comprehensive literature review. American Journal of Medical Genetics: Part A, 182 (7), 1637-1654. (doi:10.1002/ajmg.a.61599).

Record type: Article

Abstract

With advances in genetic testing and improved access to such advances, whole exome sequencing is becoming a first line investigation in clinical work-up of children with developmental delay/ intellectual disability. As a result, the need to understand the importance of genetic variants and its effect on the clinical phenotype is increasing.

Here we report on the largest cohort of patients with HNRNPU variants. These twenty one patients follow on from the previous study published by Yates et al., 2017 from our group predominantly identified from the Deciphering Developmental Disorders (DDD) study that reported seven patients with HNRNPU variants. All the probands reported here have a de novo loss-of-function variant.

These probands have craniofacial dysmorphic features, in the majority including widely spaced teeth, microcephaly, high arched eyebrows and palpebral fissure abnormalities. Many of the patients in the group also have moderate-severe intellectual disability and seizures that tend to start in early childhood.

This series has allowed us to define a novel neurodevelopmental syndrome, with a likely mechanism of haploinsufficiency, and expand substantially on already published literature on HNRNPU-related neurodevelopmental syndrome.

Text
23 3 20 AJMG-A Revision 4 HNRNPU AD^MMB edit clean copy - Accepted Manuscript
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More information

Accepted/In Press date: 24 March 2020
e-pub ahead of print date: 22 April 2021
Keywords: DDD study, HNRNPU, exome sequencing, intellectual disability, seizures

Identifiers

Local EPrints ID: 438991
URI: http://eprints.soton.ac.uk/id/eprint/438991
ISSN: 1552-4825
PURE UUID: b65463f5-179a-4e6e-835a-4837c22df6f6
ORCID for Andrew Douglas: ORCID iD orcid.org/0000-0001-5154-6714

Catalogue record

Date deposited: 31 Mar 2020 16:31
Last modified: 26 Nov 2021 02:55

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Contributors

Author: A Durkin
Author: S Albaba
Author: AE Fry
Author: Jenny E Morton
Author: Andrew Douglas ORCID iD
Author: A Beleza
Author: D Williams
Author: CML Volker-Touw
Author: S. A. Lynch
Author: N. Canham
Author: V. Clowes
Author: V. Straub
Author: Katherine Lachlan
Author: Frances Gibbon
Author: M El Gamal
Author: V Verghese
Author: M. J. Parker
Author: Ruth Newbury-Ecob
Author: Peter D. Turnpenny
Author: A Gardham
Author: N. Ghali
Author: M. Balasubramanian
Corporate Author: DDD Study

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