Jumonji domain containing 1C (JMJD1C) sequence variants in seven patients with autism spectrum disorder, intellectual disability and seizures

Anne Slavotinek*, Johanna M. van Hagen, Louisa Kalsner, Shashidhar Pai, Laura Davis-Keppen, Lisa Ohden, Yvonne G. Weber, Erica L. Macke, Eric W. Klee, Eva Morava, Lauren Gunderson, Richard Person, Shuxi Liu, Marjan Weiss

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The Jumonji domain containing 1C (JMJD1C) gene encodes the Jumonji domain-containing protein 1C (JMJD1C) and is a member of the jmJC domain-containing protein family involved in histone demethylation that is expressed in the brain. We report seven, unrelated patients with developmental delays or intellectual disability and heterozygous, de novo sequence variants in JMJD1C. All patients had developmental delays, but there were no consistent additional findings. Two patients were reported to have seizures for which there was no other identified cause. De novo, deleterious sequence variants in JMJD1C have previously been reported in patients with autism spectrum disorder and a phenotype resembling classical Rett syndrome, but only one JMJD1C variant has undergone functional evaluation. In all of the seven patients in this report, there was a plausible, alternative explanation for the neurocognitive phenotype or a modifying factor, such as an additional potentially pathogenic variant, presence of the variant in a population database, heteroplasmy for a mitochondrial variant or mosaicism for the JMJD1C variant. Although the de novo variants in JMJD1C are likely to be relevant to the developmental phenotypes observed in these patients, we conclude that further data supporting the association of JMJD1C variants with intellectual disability is still needed.

Original languageEnglish
Article number103850
JournalEuropean Journal of Medical Genetics
Issue number4
Publication statusPublished - Apr 2020

Cite this