Mutations in the JARID1C Gene, Which Is Involved in Transcriptional Regulation and Chromatin Remodeling, Cause X-Linked Mental Retardation
Open accessAbstract
In families with nonsyndromic X-linked mental retardation (NS-XLMR), >30% of mutations seem to cluster on proximal Xp and in the pericentric region. In a systematic screen of brain-expressed genes from this region in 210 families with XLMR, we identified seven different mutations in JARID1C, including one frameshift mutation and two nonsense mutations that introduce premature stop codons, as well as four missense mutations that alter evolutionarily conserved amino acids. In two of these families, expression studies revealed the almost complete absence of the mutated JARID1C transcript, suggesting that the phenotype in these families results from functional loss of the JARID1C protein. JARID1C (Jumonji AT-rich interactive domain 1C), formerly known as "SMCX," is highly similar to the Y-chromosomal gene JARID1D/SMCY, which encodes the H-Y antigen. The JARID1C protein belongs to the highly conserved ARID protein family. It contains several DNA-binding motifs that link it to transcriptional regulation and chromatin remodeling, processes that are defective in various other forms of mental retardation. Our results suggest that JARID1C mutations are a relatively common cause of XLMR and that this gene might play an important role in human brain function.
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The authors identified four dURVs in schizophrenia cases and none in controls in KDM5C, 11 in cases and 2 in controls in KDM5B, and 11 in cases and 3 in controls in ITPR1.
“we identified four dURVs in schizophrenia cases (and none in controls) in XLID gene KDM5C, an H3K4 methylation eraser gene44, 11 dURVs in cases (and 2 in controls) in DD gene KDM5B, another H3K4 methylation eraser gene45, and 11 dURVs in cases (and 3 in controls) in DD gene ITPR1, which encodes an inositol triphosphate receptor46 (Supplementary Tables 2 and 3).”
From Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia (2016) · cites this paper as [44]
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Self-citation
- Authors
- Jensen, L. R., Amende, M., Gurok, U., Moser, B., Gimmel, V., Tzschach, A., Janecke, A. R., Tariverdian, G., Chelly, J., Fryns, J.-P., Van Esch, H., Kleefstra, T., Hamel, B., Moraine, C., Gécz, J., Turner, G., Reinhardt, R., Kalscheuer, V. M., Ropers, H.-H., & Lenzner, S.
- Affiliations
- Max Planck Institute for Molecular Genetics (DE)
- Innsbruck Medical University (AT)
- Heidelberg University (DE)
- Centre National de la Recherche Scientifique (FR)
- KU Leuven (BE)
- Inserm (FR)
- Women's and Children's Hospital (AU)
- Hunter Genetics (AU)
- Corresponding author
- Lenzner, Steffen
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 76
- Issue
- 2
- Pages
- 227-236
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1196368
- OpenAlex
- W2134052811
- Cited by
- 373
- References
- 32
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 11 · 2023: 16 · 2022: 18 · 2021: 18 · 2020: 14 · 2019: 17 · 2018: 12 · 2017: 10 · 2016: 22 · 2015: 24 · 2014: 27 · 2013: 19 · 2012: 21
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- JARID1C, X-linked intellectual disability, non-syndromic intellectual disability, chromatin remodeling, transcriptional regulation, missense mutations, nonsense mutation, frameshift mutation, loss of function, brain-expressed genes, X chromosome
- MeSH terms
- Adult, Brain, Child, Child, Preschool, Chromosome Mapping, DNA Mutational Analysis, Gene Expression Regulation, Humans, Male, Intellectual Disability, Oxidoreductases, N-Demethylating, Pedigree, Phenotype, Proteins, Case-Control Studies, DNA Adducts, Genetic Diseases, X-Linked, Histone Demethylases
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