An atypical 12q24.31 microdeletion implicates six genes including a histone demethylase KDM2B and a histone methyltransferase SETD1B in syndromic intellectual disability
Abstract
Microdeletion syndromes are frequent causes of neuropsychiatric disorders leading to intellectual disability as well as autistic features accompanied by epilepsy and craniofacial anomalies. From comparative deletion mapping of the smallest microdeletion to date at 12q24.31, found in a patient with overlapping clinical features of 12q24.31 microdeletion syndrome, we narrowed the putative critical region to 445 kb containing seven genes, one microRNA, and one non-coding RNA. Zebrafish in situ hybridization and comprehensive transcript analysis of annotated genes in the panels of human organ and brain suggest that these are all candidates for neurological phenotypes excluding the gene HPD. This is also corroborated by synteny analysis revealing the conservation of the order of these six candidate genes between humans and zebrafish. Among them, we propose histone demethylase KDM2B and histone methyltransferase SETD1B as the two most plausible candidate genes involved in intellectual disability, autism, epilepsy, and craniofacial anomalies. These two chromatin modifiers located approximately 224 kb apart were both commonly deleted in six patients, while two additional patients had either KDM2B or SETD1B deleted. The four additional candidate genes (ORAI1, MORN3, TMEM120B, RHOF), a microRNA MIR548AQ, and a non-coding RNA LINC01089 are localized between KDM2B and SETD1B. The 12q24.31 microdeletion syndrome with syndromic intellectual disability extends the growing list of microdelet…
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Heterozygous Cyfip2 knockout mice present no obvious phenotype, whereas homozygous knockout mice present a phenotype similar to that of humans.
“In comparison, heterozygous KO mice present no obvious phenotype, whereas homozygous KO mice present a phenotype similar to that of humans123.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [123]
Cites
Synaptic, transcriptional and chromatin genes disrupted in autism
Study, T. D., De Rubeis, S., Autism, H. M. C. F., UK10K Consortium, The Autism Sequencing Consortium, He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Ercument Cicek, A., et al. (2014) · Nature · doi:10.1038/nature13772 · Cited by 2,746 · see citing works
JmjC-domain-containing proteins and histone demethylation
Klose, R. J., Kallin, E. M., & Zhang, Y. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1945 · Cited by 1,290 · see citing works
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders
Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., Thiruvahindrapuram, B., Xu, X., Ziman, R., Wang, Z., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.03.018 · Cited by 969 · see citing works
Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
Petrovski, S., Wang, Q., Heinzen, E. L., Allen, A. S., & Goldstein, D. B. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003709 · Cited by 901 · see citing works
From neural development to cognition: unexpected roles for chromatin
Ronan, J. L., Wu, W., & Crabtree, G. R. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3413 · Cited by 544 · see citing works
SET for life: biochemical activities and biological functions of SET domain-containing proteins
Herz, H.-M., Garruss, A., & Shilatifard, A. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.09.004 · Cited by 314 · see citing works
JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes
Frescas, D., Guardavaccaro, D., Bassermann, F., Koyama-Nasu, R., & Pagano, M. (2007) · Nature · doi:10.1038/nature06255 · Cited by 284 · see citing works
Kim, H.-G., Ahn, J.-W., Kurth, I., Ullmann, R., Kim, H.-T., Kulharya, A., Ha, K.-S., Itokawa, Y., Meliciani, I., Wenzel, W., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.08.018 · Cited by 195 · see citing works
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Zhong, Q., Xiao, X., Qiu, Y., Xu, Z., Chen, C., Chong, B., Zhao, X., Hai, S., Li, S., An, Z., et al. (2023) · MedComm · doi:10.1002/mco2.261 · Cited by 442 · see citing works
De novo variants in SETD1B are associated with intellectual disability, epilepsy and autism
Hiraide, T., Nakashima, M., Yamoto, K., Fukuda, T., Kato, M., Ikeda, H., Sugie, Y., Aoto, K., Kaname, T., Nakabayashi, K., et al. (2018) · Human Genetics · doi:10.1007/s00439-017-1863-y · Cited by 75 · see citing works
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
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- Authors
- Labonne, J. D. J., Lee, K.-H., Iwase, S., Kong, I.-K., Diamond, M. P., Layman, L. C., Kim, C.-H., & Kim, H.-G.
- Affiliations
- Augusta University (US)
- Chungnam National University (KR)
- University of Michigan (US)
- Gyeongsang National University (KR)
- Corresponding author
- Kim, Hyung-Goo
- ORCID
- Venue
- Human Genetics
- Published
- 2016-04-22
- Volume
- 135
- Issue
- 7
- Pages
- 757-771
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- OpenAlex
- W2340675305
- Cited by
- 61
- References
- 8
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 10 · 2022: 7 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 6 · 2017: 2
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS089896)
- Cooley's Anemia Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- microdeletion syndromes, syndromic intellectual disability, KDM2B, SETD1B, histone demethylase, histone methyltransferase, chromatin modifiers, autism spectrum disorder, epilepsy, craniofacial anomalies, candidate genes, zebrafish, synteny, Orai1
- MeSH terms
- Adolescent, Adult, Aged, Animals, Autistic Disorder, Chromosome Deletion, Chromosomes, Human, Pair 12, Disease Models, Animal, Epilepsy, Female, Fetus, Humans, Male, Intellectual Disability, Middle Aged, Histone-Lysine N-Methyltransferase, Zebrafish, In Situ Hybridization, Fluorescence, F-Box Proteins, Comparative Genomic Hybridization, Jumonji Domain-Containing Histone Demethylases
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