Open Access

Genotype‑phenotype analysis in Mowat‑Wilson syndrome associated with two novel and two recurrent ZEB2 variants

  • Authors:
    • Dongfang Zou
    • Lin Wang
    • Feiqiu Wen
    • Hongdou Xiao
    • Jing Duan
    • Tongda Zhang
    • Zhenzhen Yin
    • Qiwen Dong
    • Jian Guo
    • Jianxiang Liao
  • View Affiliations

  • Published online on: October 27, 2020     https://doi.org/10.3892/etm.2020.9393
  • Article Number: 263
  • Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The current study aimed to analyze the genotype‑phenotype relationship in patients with variants of zinc finger E box‑binding homeobox 2 (ZEB2), which is a gene encoding a homeobox transcription factor known to be mutated in Mowat Wilson syndrome (MWS). Whole genome sequencing (WGS) was performed in 530 children, of whom 333 had epilepsy with or without developmental delay and 197 developmental delay alone. Pathogenic variants were identified and verified using Sanger sequencing, and the disease phenotypes of the corresponding patients were analyzed for features of MWS. WGS was performed in 333 children with epilepsy, with or without developmental delays or intellectual disability and 197 children with developmental delay alone. A total of 4 unrelated patients were indicated to be heterozygous for truncating mutations in ZEB2. A total of three of these were nonsense mutations (novel Gln1072X and recurrent Trp97X and Arg921X), and one was a frameshift mutation (novel Val357Aspfs*15). The mutations have occurred de novo as confirmed by Sanger sequence comparisons in patients and their parents. All 4 patients exhibited signs of MWS, whereby the severity increased the closer a mutation was located to the amino terminus of the protein. The results suggest that the clinical outcome in MWS depends on the relative position of the truncation in the ZEB2 gene. A number of interpretations of this genotype/phenotype association are discussed in the present study.
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December-2020
Volume 20 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zou D, Wang L, Wen F, Xiao H, Duan J, Zhang T, Yin Z, Dong Q, Guo J, Liao J, Liao J, et al: Genotype‑phenotype analysis in Mowat‑Wilson syndrome associated with two novel and two recurrent <em>ZEB2</em> variants. Exp Ther Med 20: 263, 2020.
APA
Zou, D., Wang, L., Wen, F., Xiao, H., Duan, J., Zhang, T. ... Liao, J. (2020). Genotype‑phenotype analysis in Mowat‑Wilson syndrome associated with two novel and two recurrent <em>ZEB2</em> variants. Experimental and Therapeutic Medicine, 20, 263. https://doi.org/10.3892/etm.2020.9393
MLA
Zou, D., Wang, L., Wen, F., Xiao, H., Duan, J., Zhang, T., Yin, Z., Dong, Q., Guo, J., Liao, J."Genotype‑phenotype analysis in Mowat‑Wilson syndrome associated with two novel and two recurrent <em>ZEB2</em> variants". Experimental and Therapeutic Medicine 20.6 (2020): 263.
Chicago
Zou, D., Wang, L., Wen, F., Xiao, H., Duan, J., Zhang, T., Yin, Z., Dong, Q., Guo, J., Liao, J."Genotype‑phenotype analysis in Mowat‑Wilson syndrome associated with two novel and two recurrent <em>ZEB2</em> variants". Experimental and Therapeutic Medicine 20, no. 6 (2020): 263. https://doi.org/10.3892/etm.2020.9393