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

Eur J Hum Genet 2019 07 18;27(7):1081-1089. Epub 2019 Feb 18.

Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.

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.

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Source
http://dx.doi.org/10.1038/s41431-019-0366-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777464PMC
July 2019

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