Home Publications Research Grants Inventions & Patents Awards Additional Research Activities Faculties & Institutions Research Areas

De novo variants in CNOT9 cause a neurodevelopmental disorder with or without epilepsy.

von Wintzingerode L, Ben-Zeev B, Cesario C, Chan KM, Depienne C, Elpeleg O, Iascone M, Kelley WV, Nassogne MC, Niceta M, Pezzani L, Rahner N, Revencu N, Bekheirnia MR, Santiago-Sim T, Tartaglia M, Thompson ML, Trivisano M, Hentschel J, Sticht H, Abou Jamra R, Oppermann H (2023)

---

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 25

Journal Issue: 7

DOI: 10.1016/j.gim.2023.100859

Abstract

PURPOSE: The study aimed to clinically and molecularly characterize the neurodevelopmental disorder associated with heterozygous de novo variants in CNOT9. METHODS: Individuals were clinically examined. Variants were identified using exome or genome sequencing. These variants were evaluated using in silico predictions, and their functional relevance was further assessed by molecular models and research in the literature. The variants have been classified according to the criteria of the American College of Medical Genetics. RESULTS: We report on 7 individuals carrying de novo missense variants in CNOT9, p.(Arg46Gly), p.(Pro131Leu), and p.(Arg227His), and, recurrent in 4 unrelated individuals, p.(Arg292Trp). All affected persons have developmental delay/intellectual disability, with 5 of them showing seizures. Other symptoms include muscular hypotonia, facial dysmorphism, and behavioral abnormalities. Molecular modeling predicted that the variants are damaging and would lead to reduced protein stability or impaired recognition of interaction partners. Functional analyses in previous studies showed a pathogenic effect of p.(Pro131Leu) and p.(Arg227His). CONCLUSION: We propose CNOT9 as a novel gene for neurodevelopmental disorder and epilepsy.

Authors with CRIS profile

Involved external institutions

How to cite

APA:

von Wintzingerode, L., Ben-Zeev, B., Cesario, C., Chan, K.M., Depienne, C., Elpeleg, O.,... Oppermann, H. (2023). De novo variants in CNOT9 cause a neurodevelopmental disorder with or without epilepsy. Genetics in Medicine, 25(7). https://doi.org/10.1016/j.gim.2023.100859

MLA:

von Wintzingerode, Lydia, et al. "De novo variants in CNOT9 cause a neurodevelopmental disorder with or without epilepsy." Genetics in Medicine 25.7 (2023).

BibTeX: Download