Journal article

Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability

Nicole J Van Bergen, Yiran Guo, Noraldin Al-Deri, Zhanna Lipatova, Daniela Stanga, Sarah Zhao, Rakhilya Murtazina, Valeriya Gyurkovska, Davut Pehlivan, Tadahiro Mitani, Alper Gezdirici, Jayne Antony, Felicity Collins, Mary JH Willis, Zeynep H Coban Akdemir, Pengfei Liu, Jaya Punetha, Jill V Hunter, Shalini N Jhangiani, Jawid M Fatih Show all

Brain | OXFORD UNIV PRESS | Published : 2020

Abstract

The conserved transport protein particle (TRAPP) complexes regulate key trafficking events and are required for autophagy. TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes and one of the essential subunits for guanine nucleotide exchange factor activity for Rab1 GTPase. Pathogenic variants in specific TRAPP subunits are associated with neurological disorders. We undertook exome sequencing in three unrelated families of Caucasian, Turkish and French-Canadian ethnicities with seven affected children that showed features of early-onset seizures, developmental delay, microcephaly, sensorineural deafness, spastic quadriparesis and progressive cortical and cereb..

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Grants

Awarded by National Institute of General Medical Sciences (NIGMS) grant


Awarded by National Institute of Neurological Disorders and Stroke (NINDS)


Awarded by US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI)


Awarded by US National Institute of Neurological Disorders and Stroke (NINDS)


Awarded by Muscular Dystrophy Association


Funding Acknowledgements

The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. Sequencing, data analysis and Sanger validation were done in the Center for Applied Genomics at the Children's Hospital of Philadelphia through research funding from Aevi Genomic Medicine, Inc. Funding for M.S. was from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council. Funding for N.S. was from the National Institute of General Medical Sciences (NIGMS) grant GM-45444 and the National Institute of Neurological Disorders and Stroke (NINDS) grant NS-099556. This work was supported in part by the US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI) UM1 HG006542 to the Baylor Hopkins Center for Mendelian Genomics (BHCMG), the US National Institute of Neurological Disorders and Stroke (NINDS) grant R35 NS105078 to J.L. and the Muscular Dystrophy Association, grant #512848 awarded to J.L. T.M. is supported by the Uehara Memorial Foundation.