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. 2025 Jul 7:16:1616005.
doi: 10.3389/fgene.2025.1616005. eCollection 2025.

Identification of a novel microdeletion at 9q21.13 in a family with epilepsy, intellectual disability, and speech disorders and literature review

Liqing Jiang #  1   2   3 , Jiaqi Li #  1 , Aizhong Han #  1   2   3 , Fei Hou  1   2   3 , Xiaotong Wei  1 , Yanjun Tian  1   2   3
Affiliations

Identification of a novel microdeletion at 9q21.13 in a family with epilepsy, intellectual disability, and speech disorders and literature review

Liqing Jiang et al. Front Genet. .

Abstract

Background: At present, there are few reports on 9q21.13 microdeletion syndrome, which is characterized by intellectual disability, epilepsy, autistic behaviour, and recognizable facial features, etc. The aim of this study is to enrich the phenotypic features of 9q21.13 microdeletion syndrome and expand the possible segments of 9q21.13 microdeletion syndrome.

Methods: Four individuals from a 3-generation Chinese family with epilepsy, intellectual disability, and speech disorders were recruited in this study. Whole exome sequencing (WES) and chromosome microarray analysis (CMA) techniques were used for genetic testing. The pathogenicity of CNVs was interpreted following the American College of Medical Genetics (ACMG) standards and guidelines.

Results: A 9q21.13 microdeletion with a fragment size of approximately 2.35 Mb was identified in the proband, the proband's mother and grandmother and even the fetus. And this region encompasses 6 protein coding genes, namely, ALDH1A1, ANXA1, GDA, RORB, TMC1, and ZFAND5.

Conclusion: In this article, we report a girl with epilepsy, intellectual disability, speech disorders, delayed motor development, and autism. We identified a novel 9q21.13 microdeletion with a fragment size of approximately 2.35 Mb in 4 individuals from a 3-generation Chinese family by WES and CMA techniques. Within the region, the RORB gene is a strong candidate gene for complex neurodevelopmental disorders. Herein, we speculate that RORB makes a significant contribution to the clinical phenotypes caused by 9q21.13 microdeletion.

Keywords: 9q21.13 microdeletion; chromosome microarray analysis; copy number variations; epilepsy; intellectual disability; whole exome sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
CNV results of the affected family in 9q21.13. The proband, the fetus, the mother and the grandmother were all single copy in 9q21.13. The pink, green, blue, purple colors represent the proband, the fetus, the mother and the grandmother, respectively.
FIGURE 2
FIGURE 2
Segregation of 9q21.13 microdeletion in the affected family. The grandmother (Ⅰ-2), the mother (Ⅱ-2), the proband (Ⅲ-2) and even the fetus (Ⅲ-3) were detected with 9q21.13 microdeletion. Circle represents female, square represents male, and the triangle represents gender unknown. Symbols in black indicate the presence of 9q21.13 microdeletion; empty symbols represent unaffected individuals; the arrow represents the proband.
See this image and copyright information in PMC

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References

    1. André E., Conquet F., Steinmayr M., Stratton S. C., Porciatti V., Becker-André M. (1998). Disruption of retinoid-related orphan receptor beta changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice. EMBO J. 17 (14), 3867–3877. 10.1093/emboj/17.14.3867 - DOI - PMC - PubMed
    1. Baglietto M. G., Caridi G., Gimelli G., Mancardi M., Prato G., Ronchetto P., et al. (2014). RORB gene and 9q21.13 microdeletion: report on a patient with epilepsy and mild intellectual disability. Eur. J. Med. Genet. 57 (1), 44–46. 10.1016/j.ejmg.2013.12.001 - DOI - PubMed
    1. Bartnik M., Szczepanik E., Derwińska K., Wiśniowiecka-Kowalnik B., Gambin T., Sykulski M., et al. (2012). Application of array comparative genomic hybridization in 102 patients with epilepsy and additional neurodevelopmental disorders. Am. J. Med. Genet. B Neuropsychiatr. Genet. 159b (7), 760–771. 10.1002/ajmg.b.32081 - DOI - PubMed
    1. Boudry-Labis E., Demeer B., Le Caignec C., Isidor B., Mathieu-Dramard M., Plessis G., et al. (2013). A novel microdeletion syndrome at 9q21.13 characterised by mental retardation, speech delay, epilepsy and characteristic facial features. Eur. J. Med. Genet. 56 (3), 163–170. 10.1016/j.ejmg.2012.12.006 - DOI - PubMed
    1. Coppola A., Cellini E., Stamberger H., Saarentaus E., Cetica V., Lal D., et al. (2019). Diagnostic implications of genetic copy number variation in epilepsy plus. Epilepsia 60 (4), 689–706. 10.1111/epi.14683 - DOI - PMC - PubMed

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