OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: <em>De novo</em> nonsense and frameshift variants of <em>TCF20</em> in individuals with intellectual disability and postnatal overgrowth.

PuSH - Publication Server of Helmholtz Zentrum München

Schäfgen, J.* ; Cremer, K.* ; Becker, J.* ; Wieland, T. ; Zink, A.M.* ; Kim, S.* ; Windheuser, I.C.* ; Kreiß, M.* ; Aretz, S.* ; Strom, T.M. ; Wieczorek, D.* ; Engels, H.*

De novo nonsense and frameshift variants of TCF20 in individuals with intellectual disability and postnatal overgrowth.

Eur. J. Hum. Genet. 24, 1739-1745 (2016)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Recently, germline variants of the transcriptional co-regulator gene TCF20 have been implicated in the aetiology of autism spectrum disorders (ASD). However, the knowledge about the associated clinical picture remains fragmentary. In this study, two individuals with de novo TCF20 sequence variants were identified in a cohort of 313 individuals with intellectual disability of unknown aetiology, which was analysed by whole exome sequencing using a child-parent trio design. Both detected variants - one nonsense and one frameshift variant - were truncating. A comprehensive clinical characterisation of the patients yielded mild intellectual disability, postnatal tall stature and macrocephaly, obesity and muscular hypotonia as common clinical signs while ASD was only present in one proband. The present report begins to establish the clinical picture of individuals with de novo nonsense and frameshift variants of TCF20 which includes features such as proportionate overgrowth and muscular hypotonia. Furthermore, intellectual disability/developmental delay seems to be fully penetrant amongst known individuals with de novo nonsense and frameshift variants of TCF20, whereas ASD is shown to be incompletely penetrant. The transcriptional co-regulator gene TCF20 is hereby added to the growing number of genes implicated in the aetiology of both ASD and intellectual disability. Furthermore, such de novo variants of TCF20 may represent a novel differential diagnosis in the overgrowth syndrome spectrum.
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Autism Spectrum; Mental Deficiency; Mutations; Abnormalities; Prevalence; Disorders; Transcription; Children; Domains; Genes
ISSN (print) / ISBN 1018-4813
e-ISSN 1476-5438
Journal European Journal of Human Genetics
Quellenangaben Volume: 24, Issue: 12, Pages: 1739-1745 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)