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 - Funding Information:
Acknowledgements We thank families for their generous contribution. This work was supported in part by a grant from the Simons Foundation and the JPB Foundation. This work was supported in part by grants from the National Eye Institute [RO1EY012910 (EAP), R01EY026904 (KMB/EAP) and P30EY014104 (MEEI core support)], the Foundation Fighting Blindness (USA, EAP). Sequencing and analysis of samples from MEEI was provided by the Center for Mendelian Genomics at the Broad Institute of MIT and Harvard and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 to Daniel MacArthur and Heidi Rehm.
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
VL - 27
SP - 1081
EP - 1089
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 7
ER -