Journal article

NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism

Hui Guo, Qiumeng Zhang, Rujia Dai, Bin Yu, Kendra Hoekzema, Jieqiong Tan, Senwei Tan, Xiangbin Jia, Wendy K Chung, Rebecca Hernan, Fowzan S Alkuraya, Ahood Alsulaiman, Mohammad A Al-Muhaizea, Gaetan Lesca, Linda Pons, Audrey Labalme, Linda Laux, Emily Bryant, Natasha J Brown, Elena Savva Show all

American Journal of Human Genetics | CELL PRESS | Published : 2020


NCKAP1/NAP1 regulates neuronal cytoskeletal dynamics and is essential for neuronal differentiation in the developing brain. Deleterious variants in NCKAP1 have been identified in individuals with autism spectrum disorder (ASD) and intellectual disability; however, its clinical significance remains unclear. To determine its significance, we assemble genotype and phenotype data for 21 affected individuals from 20 unrelated families with predicted deleterious variants in NCKAP1. This includes 16 individuals with de novo (n = 8), transmitted (n = 6), or inheritance unknown (n = 2) truncating variants, two individuals with structural variants, and three with potentially disruptive de novo missens..

View full abstract


Awarded by National Natural Science Foundation of China

Awarded by US National Institutes of Health (NIH)

Awarded by Hunan Provincial grants

Awarded by Innovation-Driven Project of Central South University

Awarded by Swiss National Science Foundation

Funding Acknowledgements

We are grateful to the families involved in this study. We thank Tonia Brown for assistance in editing this manuscript. We thank Mais Hashem, Egidio Spinelli, and John J. Millichap for coordinating data collection. Thisworkwas supported by the following grants: theNational Natural Science Foundation of China (81871079, 81330027, 81525007, 8173000779, 81671122) to H.G., K.X., and Z.H.; The US National Institutes of Health (NIH) grant (MH101221) to E.E.E.; and the Hunan Provincial grants (2018SK1030, 2018DK2016, 2019SK1015, 2019RS2005) to K.X., Z.H., and H.G. H.G. was also supported by the Innovation-Driven Project of Central South University (2020CX042). N.J.B., E.S., S.A., and D.E. was supported by the State Government of Victoria (Department of Health and Human Services, Melbourne Genomics Health Alliance). J.M.M. and F.S. are supported by the Swiss National Science Foundation (310030_185292). W.K.C. is supported by grants from the Simons Foundation and the JPB Foundation. E.E.E. is an investigator of the Howard Hughes Medical Institute.