university website

Konrad, E.D.H. (Enrico D. H.), Nardini, N. (Niels), Caliebe, A. (Almuth), Nagel, I. (Inga), Young, D. (Dana), Horvath, G. (Gabriella), Santoro, S.L. (Stephanie L.), Shuss, C. (Christine), Ziegler, A. (Alban), D. Bonneau (Dominique), et al. M.J.E. Kempers (Marlies), R. Pfundt (Rolph), E. Legius (Eric), A. Bouman (Arjan), Stuurman, K.E. (Kyra E.), K. Õunap (Katrin), Pajusalu, S. (Sander), Wojcik, M.H. (Monica H.), Vasileiou, G. (Georgia), Le Guyader, G. (Gwenaël), Schnelle, H.M. (Hege M.), Berland, S. (Siren), Zonneveld-Huijssoon, E. (Evelien), Kersten, S. (Simone), Gupta, A. (Aditi), Blackburn, P.R. (Patrick R.), Ellingson, M.S. (Marissa S.), Ferber, M.J. (Matthew J.), Dhamija, R. (Radhika), Klee, E.W. (Eric W.), M. McEntagart (Meriel), K.D. Lichtenbelt (Klaske), Kenney, A. (Amy), Vergano, S.A. (Samantha A.), Abou Jamra, R. (Rami), Platzer, K. (Konrad), Ella Pierpont, M. (Mary), Khattar, D. (Divya), R. Hopkin, Martin, R.J. (Richard J.), M.C.J. Jongmans (Marjolijn), Chang, V.Y. (Vivian Y.), Martinez-Agosto, J.A. (Julian A.), Kuismin, O. (Outi), Kurki, M.I. (Mitja I.), O.P.H. Pietiläinen (Olli), A. Palotie (Aarno), Maarup, T.J. (Timothy J.), D. Johnson (David), Venborg Pedersen, K. (Katja), Laulund, L.W. (Lone W.), Lynch, S.A. (Sally A.), Blyth, M. (Moira), K. Prescott (Katrina), N. Canham (Natalie), Ibitoye, R. (Rita), Brilstra, E.H. (Eva H.), Shinawi, M. (Marwan), Fassi, E. (Emily), H. Sticht (Heinrich), Gregor, A. (Anne), H. van Esch (Hilde) and C. Zweier (Christiane)

2019-06-26

CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum

Publication

Publication

Genetics in Medicine

Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.

Additional Metadata
Keywords chromatin organization, CTCF, Drosophila melanogaster, intellectual disability, neurodevelopmental disorders
Persistent URL doi.org/10.1038/s41436-019-0585-z, hdl.handle.net/1765/117622
Journal Genetics in Medicine
Organisation Erasmus MC: University Medical Center Rotterdam
Citation
Konrad, E.D.H. (Enrico D. H.), Nardini, N. (Niels), Caliebe, A. (Almuth), Nagel, I. (Inga), Young, D. (Dana), Horvath, G. (Gabriella), … Zweier, C. (2019). CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum. Genetics in Medicine. doi:10.1038/s41436-019-0585-z
Free Full Text ( Final Version , 2mb ) cover


User Publication Person Organisation Collection
Close