Open Access

Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay

  • Authors:
    • Marketa Wayhelova
    • Jan Oppelt
    • Jan Smetana
    • Eva Hladilkova
    • Hana Filkova
    • Eva Makaturova
    • Petra Nikolova
    • Rastislav Beharka
    • Renata Gaillyova
    • Petr Kuglik
  • View Affiliations

  • Published online on: May 27, 2019     https://doi.org/10.3892/mmr.2019.10303
  • Pages: 505-512
  • Copyright : © Wayhelova et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

De novo sequence variants, including truncating and splicing variants, in the additional sex‑combs like 3 gene (ASXL3) have been described as the cause of Bainbridge‑Ropers syndrome (BRS). This pathology is characterized by delayed psychomotor development, severe intellectual disability, growth delay, hypotonia and facial dimorphism. The present study reports a case of a girl (born in 2013) with severe global developmental delay, central hypotonia, microcephaly and poor speech. The proband was examined using a multi‑step molecular diagnostics algorithm, including karyotype and array‑comparative genomic hybridization analysis, with negative results. Therefore, the proband and her unaffected parents were enrolled for a pilot study using targeted next‑generation sequencing technology (NGS) with gene panel ClearSeq Inherited DiseaseXT and subsequent validation by Sanger sequencing. A novel de novo heterozygous frameshift variant in the ASXL3 gene (c.3006delT, p.R1004Efs*21), predicted to result in a premature termination codon, was identified. In conclusion, the present study demonstrated that targeted NGS using a suitable, gene‑rich panel may provide a conclusive molecular genetics diagnosis in children with severe global developmental delays.
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July-2019
Volume 20 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wayhelova M, Oppelt J, Smetana J, Hladilkova E, Filkova H, Makaturova E, Nikolova P, Beharka R, Gaillyova R, Kuglik P, Kuglik P, et al: Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay. Mol Med Rep 20: 505-512, 2019
APA
Wayhelova, M., Oppelt, J., Smetana, J., Hladilkova, E., Filkova, H., Makaturova, E. ... Kuglik, P. (2019). Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay. Molecular Medicine Reports, 20, 505-512. https://doi.org/10.3892/mmr.2019.10303
MLA
Wayhelova, M., Oppelt, J., Smetana, J., Hladilkova, E., Filkova, H., Makaturova, E., Nikolova, P., Beharka, R., Gaillyova, R., Kuglik, P."Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay". Molecular Medicine Reports 20.1 (2019): 505-512.
Chicago
Wayhelova, M., Oppelt, J., Smetana, J., Hladilkova, E., Filkova, H., Makaturova, E., Nikolova, P., Beharka, R., Gaillyova, R., Kuglik, P."Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay". Molecular Medicine Reports 20, no. 1 (2019): 505-512. https://doi.org/10.3892/mmr.2019.10303