TY - JOUR
T1 - De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment
AU - Okur, Volkan
AU - Cho, Megan T.
AU - van Wijk, Richard
AU - van Oirschot, Brigitte
AU - Picker, Jonathan
AU - Coury, Stephanie A.
AU - Grange, Dorothy
AU - Manwaring, Linda
AU - Krantz, Ian
AU - Muraresku, Colleen Clark
AU - Hulick, Peter J.
AU - May, Holley
AU - Pierce, Eric
AU - Place, Emily
AU - Bujakowska, Kinga
AU - Telegrafi, Aida
AU - Douglas, Ganka
AU - Monaghan, Kristin G.
AU - Begtrup, Amber
AU - Wilson, Ashley
AU - Retterer, Kyle
AU - Anyane-Yeboa, Kwame
AU - Chung, Wendy K.
N1 - Publisher Copyright:
© 2019, European Society of Human Genetics.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061719602&partnerID=8YFLogxK
U2 - 10.1038/s41431-019-0366-9
DO - 10.1038/s41431-019-0366-9
M3 - Article
C2 - 30778173
AN - SCOPUS:85061719602
SN - 1018-4813
VL - 27
SP - 1081
EP - 1089
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 7
ER -