Poole, Rebecca L;
Badonyi, Mihaly;
Cozens, Alison;
Foulds, Nicola;
Marsh, Joseph A;
Rahman, Shamima;
Ross, Alison;
... Lampe, Anne; + view all
(2023)
Expanding the neurodevelopmental phenotype associated with HK1 de novo heterozygous missense variants.
European Journal of Medical Genetics
, 66
(3)
, Article 104696. 10.1016/j.ejmg.2023.104696.
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Abstract
Neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA) is a recently described genetic condition caused by de novo missense HK1 variants. Phenotypic data is currently limited; only seven patients have been published to date. This descriptive case series of a further four patients with de novo missense HK1 variants, alongside integration of phenotypic data with the reported cases, aims to improve our understanding of the associated phenotype. We provide further evidence that de novo HK1 variants located within the regulatory-terminal domain and alpha helix are associated with neurological problems and visual problems. We highlight for the first time an association with a raised cerebrospinal fluid lactate and specific abnormalities to the basal ganglia on brain magnetic resonance imaging, as well as associated respiratory issues and swallowing/feeding difficulties. We propose that this distinctive neurodevelopmental phenotype could arise through disruption of the regulatory glucose-6-phosphate binding site and subsequent gain of function of HK1 within the brain.
| Type: | Article |
|---|---|
| Title: | Expanding the neurodevelopmental phenotype associated with HK1 de novo heterozygous missense variants |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejmg.2023.104696 |
| Publisher version: | https://doi.org/10.1016/j.ejmg.2023.104696 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Basal ganglia, Disorder, HK1 protein, Human, Neurological |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10163418 |
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