Journal article
Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia
J Wan, J Steffen, M Yourshaw, H Mamsa, E Andersen, S Rudnik-Schöneborn, K Pope, KB Howell, CA Mclean, AJ Kornberg, J Joseph, PJ Lockhart, K Zerres, MM Ryan, SF Nelson, CM Koehler, JC Jen
Brain | OXFORD UNIV PRESS | Published : 2016
DOI: 10.1093/brain/aww212
Abstract
Disturbed mitochondrial fusion and fission have been linked to various neurodegenerative disorders. In siblings from two unrelated families who died soon after birth with a profound neurodevelopmental disorder characterized by pontocerebellar hypoplasia and apnoea, we discovered a missense mutation and an exonic deletion in the SLC25A46 gene encoding a mitochondrial protein recently implicated in optic atrophy spectrum disorder. We performed functional studies that confirmed the mitochondrial localization and pro-fission properties of SLC25A46. Knockdown of slc24a46 expression in zebrafish embryos caused brain malformation, spinal motor neuron loss, and poor motility. At the cellular level, ..
View full abstractGrants
Awarded by National Institute of Neurological Disorders and Stroke
Funding Acknowledgements
This research was supported by Deutsche Forschungsgemeinschaft (DFG) STE 2045/1-1 to J.S.; Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence Grant ID 1031893 to M.M.R.; NHMRC Career Development Fellowship GNT1032364 to P.J.L. and Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS; NIH R01 GM61721 and CIRM RT307678 to C.M.K.; NIH R01 NS064183, National Center for Advancing Translational Sciences UCLA CTSI Grant UL1TR000124 and UCLA Children's Discovery and Innovation Institute Award, and the Gochman Fund to J.C.J.