Epilepsy, cognitive deficits and neuroanatomy in males with ZDHHC9 mutationsReport as inadecuate


Epilepsy, cognitive deficits and neuroanatomy in males with ZDHHC9 mutations


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Publication Date: 2015-04-09

Journal Title: Annals of Clinical and Translational Neurology

Publisher: Wiley on behalf of American Neurological Association

Volume: 2

Issue: 5

Pages: 559-569

Language: English

Type: Article

Metadata: Show full item record

Citation: Baker, K., Astle, D. E., Scerif, G., Barnes, J., Smith, J., Moffat, G., Gillard, J., et al. (2015). Epilepsy, cognitive deficits and neuroanatomy in males with ZDHHC9 mutations. Annals of Clinical and Translational Neurology, 2 (5), 559-569.

Description: This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/acn3.196/full.

Abstract: Objective Systematic investigation of individuals with intellectual disability after genetic diagnosis can illuminate specific phenotypes and mechanisms relevant to common neurodevelopmental disorders. We report the neurological, cognitive and neuroanatomical characteristics of nine males from three families with loss-of-function mutations in ZDHHC9 (OMIM #300799). Methods All known cases of X-linked intellectual disability (XLID) due to ZDHHC9 mutation in the United Kingdom were invited to participate in a study of neurocognitive and neuroimaging phenotypes. Results Seven out of nine males with ZDHHC9 mutations had been diagnosed with epilepsy, exceeding epilepsy risk in XLID comparison subjects (P = 0.01). Seizure histories and EEG features amongst ZDHHC9 mutation cases shared characteristics with rolandic epilepsy (RE). Specific cognitive deficits differentiated males with ZDHHC9 mutations from XLID comparison subjects and converged with reported linguistic and nonlinguistic deficits in idiopathic RE: impaired oromotor control, reduced verbal fluency, and impaired inhibitory control on visual attention tasks. Consistent neuroanatomical abnormalities included thalamic and striatal volume reductions and hypoplasia of the corpus callosum. Interpretation Mutations in ZDHHC9 are associated with susceptibility to focal seizures and specific cognitive impairments intersecting with the RE spectrum. Neurocognitive deficits are accompanied by consistent abnormalities of subcortical structures and inter-hemispheric connectivity. The biochemical, cellular and network-level mechanisms responsible for the ZDHHC9-associated neurocognitive phenotype may be relevant to cognitive outcomes in RE.

Sponsorship: This study was funded by the Wellcome Trust/Academy of Medical Sciences (Starter Grant for Clinical Lecturers to K. B.). K. B. is funded by the National Institute of Health Research (Academic Clinical Lectureship). J. B. and D. A. are funded by an MRC UK intramural programme (MCA0606- 5PQ41). G. S. is funded by Wellcome Trust project grant (WT079326AIA) and a James S. McDonnell Foundation Understanding Human Cognition Scholar Award. F. L. R. is funded by the National Institute of Health Research (Cambridge Biomedical Research Centre).

Identifiers:

This record's URL: http://dx.doi.org/10.1002/acn3.196http://www.repository.cam.ac.uk/handle/1810/247865

Rights: Attribution 2.0 UK: England & Wales

Licence URL: http://creativecommons.org/licenses/by/2.0/uk/





Author: Baker, KateAstle, Duncan E.Scerif, GaiaBarnes, JessicaSmith, JennieMoffat, GeorginaGillard, JonathanBaldeweg, TorstenRaymond, F. L

Source: https://www.repository.cam.ac.uk/handle/1810/247865



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