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Global developmental delay, systemic dysmorphism and epilepsy in a patient with a de novo U2AF2 variant

Journal of Human Genetics volume 66, pages 1185–1187 (2021)Cite this article

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Abstract

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor in an early step of splicing. Alternative splicing plays an important role in neuronal development, and disorders of RNA processing steps are implicated in neurological disorders. Recently, the large trio whole-exome sequencing study reported U2AF2 as a novel gene significantly associated with developmental disorders: however, the clinical details of patients with U2AF2 variants were not available. Here, we report an individual with a de novo U2AF2 variant (c.445C>T, p.(Arg149Trp)) using trio-based whole-exome sequencing. This residue was positioned in the RNA recognition motif 1 which recognizes a polypyrimidine-tract splice site signal. The patient showed global developmental delay, intellectual disability, epilepsy, short stature, microcephaly, facial dysmorphism, intermittent exotropia, bilateral ptosis, muscle hypotonia and thin corpus callosum, indicating that U2AF2-related disorder could include systemic dysmorphisms, epilepsy and brain malformation along with global developmental delay.

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Acknowledgements

We would like to thank the patients’ families for participating in this work. This work was supported by the Japan Agency for Medical Research and Development (AMED) (JP19ek0109297 to HS, and JP20ek0109301 to TO), the Grants-in-Aid for Scientific Research (B) (JP20H03641) and the Takeda Science Foundation.

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Authors and Affiliations

  1. Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Takuya Hiraide, Yohei Masunaga, Tokiko Fukuda & Tsutomu Ogata

  2. Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Takuya Hiraide, Mitsuko Nakashima, Tsutomu Ogata & Hirotomo Saitsu

  3. Department of Pediatrics, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan

    Taihei Tanaka

  4. Department of Pediatrics, Shizuoka Saiseikai Hospital, Shizuoka, Japan

    Yumiko Ohkubo

  5. Department of Pediatrics, Hamamatsu Medical Center, Hamamatsu, Japan

    Tsutomu Ogata

Authors
  1. Takuya Hiraide
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  2. Taihei Tanaka
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  3. Yohei Masunaga
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  4. Yumiko Ohkubo
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  5. Mitsuko Nakashima
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  6. Tokiko Fukuda
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  7. Tsutomu Ogata
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  8. Hirotomo Saitsu
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Correspondence to Hirotomo Saitsu.

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Hiraide, T., Tanaka, T., Masunaga, Y. et al. Global developmental delay, systemic dysmorphism and epilepsy in a patient with a de novo U2AF2 variant. J Hum Genet 66, 1185–1187 (2021). https://doi.org/10.1038/s10038-021-00948-4

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