Journal article

Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia

Kamal Khan, Michael Zech, Angela T Morgan, David J Amor, Matej Skorvanek, Tahir N Khan, Michael S Hildebrand, Victoria E Jackson, Thomas S Scerri, Matthew Coleman, Kristin A Rigbye, Ingrid E Scheffer, Melanie Bahlo, Matias Wagner, Daniel D Lam, Riccardo Berutti, Petra Havrankova, Anna Fecikova, Tim M Strom, Vladimir Han Show all

Genetics in Medicine | NATURE PUBLISHING GROUP | Published : 2019


PURPOSE: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C2H2 domain-containing transcription factor. METHODS: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals. RESULTS: We identified seven affected females i..

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Awarded by National Institutes of Health

Awarded by Czech Science Foundation

Awarded by Charles University, Prague, Czech Republic

Awarded by Slovak Grant and Development Agency

Awarded by DFG

Awarded by Australian National Health & Medical Research Council (NHMRC)

Awarded by Centre of Research Excellence

Awarded by NHMRC

Funding Acknowledgements

We are grateful to the patient families for their engagement and support of our research. We thank J. Willer for assistance with ES library prep (family C). This work was supported by grants from the National Institutes of Health (P50DK096415 to N.K. and MH106826 to E.E.D.). This study was funded in part by the Czech Science Foundation (GACR16-13323S) as well as in-house institutional funding from Technische Universitat Munchen, Munich, Germany; Helmholtz Zentrum Munchen, Munich, Germany; and Charles University, Prague, Czech Republic (PROGRES Q27). This study was also supported by the Slovak Grant and Development Agency under contract APVV-14-0415 to M.S., V.H., and Z.G. Additionally, K.K. was funded by an International Research Support Initiative Program fellowship from the Higher Education Commission of Pakistan. M.Z. was supported by an internal research program at Helmholtz Center Munich, Germany (Physician Scientists for Groundbreaking Projects). D.D.L. was supported by DFG grant LA 3830/1-1. This work was also supported by Australian National Health & Medical Research Council (NHMRC) Project (ID: 1127144) and Centre of Research Excellence (ID: 1116976) grants to A.T.M., and the Victorian Government's Operational Infrastructure Support Program and NHMRC Independent Research Institute Infrastructure Support Scheme (NHMRC IRIISS) to M.B. A.T.M. was supported by NHMRC Practitioner Fellowship 1105008. M.B. was supported by an NHMRC program grant (ID: 1054618) and NHMRC Senior Research Fellowship (ID: 1102971). M.S.H. was supported by an NHMRC Career Development Fellowship (ID:1063799).