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Khan, K.* ; Zech, M. ; Morgan, A.T.* ; Amor, D.J.* ; Škorvánek, M.* ; Khan, T.N.* ; Hildebrand, M.S.* ; Jackson, V.E.* ; Scerri, T.S.* ; Coleman, M.* ; Rigbye, K.A.* ; Scheffer, I.E.* ; Bahlo, M.* ; Wagner, M. ; Lam, D.D. ; Berutti, R. ; Havránková, P.* ; Fečíková, A.* ; Strom, T.M. ; Han, V.* ; Dosekova, P.* ; Gdovinova, Z.* ; Laccone, F.* ; Jameel, M.* ; Mooney, M.R.* ; Baig, S.M.* ; Jech, R.* ; Davis, E.E.* ; Katsanis, N.* ; Winkelmann, J.

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

Genet. Med. 21, 2532-2542 (2019)
Verlagsversion Preprint Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 C 2 H 2 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 in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia. Conclusion: Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ataxia ; Childhood Apraxia Of Speech ; Developmental Delay ; Dolichocephaly ; Homozygosity Mapping
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 1530-0366
e-ISSN 1098-3600
Zeitschrift Genetics in Medicine
Quellenangaben Band: 21, Heft: 11, Seiten: 2532-2542 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Baltimore, Md.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Institute of Human Genetics (IHG)
POF Topic(s) 30205 - Bioengineering and Digital Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-503200-001
G-500700-001
DOI 10.1038/s41436-019-0523-0
Scopus ID 85065170293
PubMed ID 31036918
Erfassungsdatum 2019-05-13
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