Abstract
ZNF711 is one of eleven zinc-finger genes on the X chromosome that have been associated with X-linked intellectual disability. This association is confirmed by the clinical findings in 20 new cases in addition to 11 cases previously reported. No consistent growth aberrations, craniofacial dysmorphology, malformations or neurologic findings are associated with alterations in ZNF711. The intellectual disability is typically mild and coexisting autism occurs in half of the cases. Carrier females show no manifestations. A ZNF711-specific methylation signature has been identified which can assist in identifying new cases and in confirming the pathogenicity of variants in the gene.
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Data availability
The summarized, anonymized data for each subject in this study are described in the text. Publicly available DNA methylation datasets have been deposited in GEO, and include data referring to various developmental syndromes (e.g., Kabuki syndrome, Sotos syndrome, CHARGE syndrome, immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, Williams- Beuren syndrome, Chr7q11.23 duplication syndrome, BAFopathies, Down syndrome), a large cohort of unresolved subjects with developmental delay/intellectual disability and congenital abnormalities, and also several large cohorts of DNA methylation data from the general population. Data in the EpiSign Knowledge Database, including methylation data from this ZNF711 study cohort, are not available due to Research Ethics Board and institutional restrictions. EpiSignTM is proprietary software and is not publicly available.
Change history
01 December 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41431-023-01499-2
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Acknowledgements
We thank members of the families for participating in this research. Dedicated to the memory of Ethan Francis Schwartz, 1996–1998. Funding for this research was provided, in part, by NIH grant HD-26202 to CES, Curekids New Zealand to SPR, the Wellcome Trust Sanger Institute, the Greenwood Genetic Center Foundation, the South Carolina Department of Disabilities and Special Needs, and the London Health Sciences Molecular Diagnostics Development Fund and Genome Canada Genomic Applications Partnership Program Grant awarded to BS (Beyond Genomics: Assessing the Improvement in Diagnosis of Rare Diseases using Clinical Epigenomics in Canada, EpiSign-CAN).
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Wang, J., Foroutan, A., Richardson, E. et al. Clinical findings and a DNA methylation signature in kindreds with alterations in ZNF711. Eur J Hum Genet 30, 420–427 (2022). https://doi.org/10.1038/s41431-021-01018-1
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DOI: https://doi.org/10.1038/s41431-021-01018-1
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