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Case Reports
. 2025 Dec;108(6):731-741.
doi: 10.1111/cge.14781. Epub 2025 Jun 30.

Six New Cases of 22q13.2 Gain Including TFC20: First Report of Triplication and Smallest Duplication Associated With Neurodevelopmental Delays

Etienne Bizot  1 , Dima Jouni  2 , Caroline Rooryck  3 , Juliet Taylor  4 , Marine Legendre  3 , Lorelei Charbonnier  1 , Julia Metreau  1   5 , Emmanuelle Benaloun  2 , Audrey Pinson  2 , Geneviève Quenum  2 , Jérôme Bouligand  2   6   7 , Gérard Tachdjian  2   6 , Philippe Labrune  1   6 , Lucie Tosca  2   6   7
Affiliations
Case Reports

Six New Cases of 22q13.2 Gain Including TFC20: First Report of Triplication and Smallest Duplication Associated With Neurodevelopmental Delays

Etienne Bizot et al. Clin Genet. 2025 Dec.

Abstract

To date, only one study describes three unrelated cases of neurodevelopmental disorders associated with duplications in 22q13.2, which include the TCF20 gene. In contrast, TCF20 variants and deletions are well characterized. Here, we report six new cases of 22q13.2 gain, including TCF20, identified through array-comparative genomic hybridization (array-CGH). Probands exhibited neurodevelopmental delay, and several presented with facial dysmorphism, abnormal growth parameters, and abnormalities affecting the skeletal, respiratory, genitourinary, and/or cardiovascular systems. We documented one 440 Kb triplication and five cases of duplication ranging from 82.5 Kb to 3.03 Mb in size. Co-segregation analysis of the CNV and clinical symptoms supports variable expressivity. However, the complete penetrance of these gains remains questionable compared to the known pathogenic variants and structural variations associated with loss of function. We discuss the genotype-phenotype correlations and hypotheses surrounding the impairment of TCF20 protein function.

Keywords: TCF20; 22q13.2; duplication; neurodevelopmental disorder; triplication.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Map of the nine gains of the 22q13.2 region and TCF20 gene, according to the UCSC, February 2009 (hg19).
See this image and copyright information in PMC

References

    1. Lévy J., Cogan G., Maruani A., et al., “Rare and de Novo Duplications Containing TCF20 Are Associated With a Neurodevelopmental Disorder,” Clinical Genetics 101, no. 3 (2022): 364–370, 10.1111/cge.14099. - DOI - PubMed
    1. Feng C., Zhao J., Ji F., Su L., Chen Y., and Jiao J., “TCF20 Dysfunction Leads to Cortical Neurogenesis Defects and Autistic‐Like Behaviors in Mice,” EMBO Reports 21, no. 8 (2020): e49239, 10.15252/embr.201949239. - DOI - PMC - PubMed
    1. Baldan F., Demori E., Gnan C., et al., “Chromoanagenesis of Chromosome 22 in a Subject With Obesity and Borderline Cognitive Performance,” Gene 933 (2024): 148956, 10.1016/j.gene.2024.148956. - DOI - PubMed
    1. Huang S., Xu J., Li Y., et al., “A Syndrome Featuring Developmental Disorder of the Nervous System Induced by a Novel Mutation in the TCF20 Gene, Rarely Concurrent Immune Disorders: A Case Report,” Frontiers in Genetics 14 (2023): 1192668, 10.3389/fgene.2023.1192668. - DOI - PMC - PubMed
    1. Schneeweiss M. R., Dale B., and Ejaz R., “Diagnosis and Clinical Presentation of Two Individuals With a Rare TCF20 Pathogenic Variant,” BMJ Case Reports 15, no. 12 (2022): e248995, 10.1136/bcr-2022-248995. - DOI - PMC - PubMed

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