Journal article

Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery

Raman Kumar, Alison Gardner, Claire C Homan, Evelyn Douglas, Heather Mefford, Dagmar Wieczorek, Hermann-Josef Luedecke, Zornitza Stark, Simon Sadedin, Catherine Bearce Nowak, Jessica Douglas, Gretchen Parsons, Paul Mark, Lourdes Loidi, Gail E Herman, Theresa Mihalic Mosher, Meredith K Gillespie, Lauren Brady, Mark Tarnopolsky, Irene Madrigal Show all

HUMAN MUTATION | WILEY | Published : 2018


Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and three maternally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and..

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Awarded by National Health and Medical Research Council Program

Awarded by Fondo de Investigacion Sanitaria

Awarded by Spanish Ministry of Economy and Competitiveness

Awarded by MINECO Severo Ochoa

Awarded by National Heart, Lung and Blood Institute


Funding Acknowledgements

Contract grant sponsors: National Health and Medical Research Council Program (APP1091593, APP1041920); Channel 7 Children's Research Foundation; Fondo de Investigacion Sanitaria (APP19PI10/01710); Spanish Ministry of Economy and Competitiveness (SEV-2016-0571); MINECO Severo Ochoa (SVP-2013-0680066); Genome Canada; National Heart, Lung and Blood Institute (UM1 HG008900); Canadian Institutes of Health Research (CIHR); Ontario Genomics Institute; Ontario Research Fund; Genome Quebec; Children's Hospital of Eastern Ontario Foundation; National Human Genome Research Institute; National Eye Institute; Undiagnosed Diseases Program-Victoria (UDP-Vic); Murdoch Children's Research Institute, Melbourne, Australia.