De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.

TitleDe novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.
Publication TypeJournal Article
Year of Publication2019
AuthorsOkur, V, Cho, MT, van Wijk, R, van Oirschot, B, Picker, J, Coury, SA, Grange, D, Manwaring, L, Krantz, I, Muraresku, CClark, Hulick, PJ, May, H, Pierce, E, Place, E, Bujakowska, K, Telegrafi, A, Douglas, G, Monaghan, KG, Begtrup, A, Wilson, A, Retterer, K, Anyane-Yeboa, K, Chung, WK
JournalEur J Hum Genet
Volume27
Issue7
Pagination1081-1089
Date Published2019 Jul
ISSN1476-5438
Abstract

Hexokinase 1 (HK1) phosphorylates glucose to glucose-6-phosphate, the first rate-limiting step in glycolysis. Homozygous and heterozygous variants in HK1 have been shown to cause autosomal recessive non-spherocytic hemolytic anemia, autosomal recessive Russe type hereditary motor and sensory neuropathy, and autosomal dominant retinitis pigmentosa (adRP). We report seven patients from six unrelated families with a neurodevelopmental disorder associated with developmental delay, intellectual disability, structural brain abnormality, and visual impairments in whom we identified four novel, de novo missense variants in the N-terminal half of HK1. Hexokinase activity in red blood cells of two patients was normal, suggesting that the disease mechanism is not due to loss of hexokinase enzymatic activity.

DOI10.1038/s41431-019-0366-9
Alternate JournalEur. J. Hum. Genet.
PubMed ID30778173
Grant ListR01 EY012910 / EY / NEI NIH HHS / United States
R01 EY026904 / EY / NEI NIH HHS / United States
UM1 HG008900 / HG / NHGRI NIH HHS / United States