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

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 neuropa...

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Bibliographic Details
Published in:	European journal of human genetics : EJHG Vol. 27; no. 7; pp. 1081 - 1089
Main Authors:	Okur, Volkan, Cho, Megan T, van Wijk, Richard, van Oirschot, Brigitte, Picker, Jonathan, Coury, Stephanie A, Grange, Dorothy, Manwaring, Linda, Krantz, Ian, Muraresku, Colleen Clark, Hulick, Peter J, May, Holley, Pierce, Eric, Place, Emily, Bujakowska, Kinga, Telegrafi, Aida, Douglas, Ganka, Monaghan, Kristin G, Begtrup, Amber, Wilson, Ashley, Retterer, Kyle, Anyane-Yeboa, Kwame, Chung, Wendy K
Format:	Journal Article
Language:	English
Published:	England Nature Publishing Group 01-07-2019 Springer International Publishing
Subjects:	Adolescent Adult Blindness Child Enzymatic activity Erythrocytes Erythrocytes - enzymology Erythrocytes - pathology Female Glycolysis Hemolytic anemia Hereditary Sensory and Motor Neuropathy - enzymology Hereditary Sensory and Motor Neuropathy - genetics Hereditary Sensory and Motor Neuropathy - pathology Hexokinase Hexokinase - genetics Hexokinase - metabolism Humans Infant Male Mutation, Missense Neurodevelopmental disorders Neuropathy Pedigree Retinitis Retinitis pigmentosa Retinitis Pigmentosa - enzymology Retinitis Pigmentosa - genetics Retinitis Pigmentosa - pathology
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1018-4813 1476-5438
DOI:	10.1038/s41431-019-0366-9