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Autosomal dominant familial acanthosis nigricans caused by a C-terminal nonsense mutation of FGFR3

Journal of Human Genetics volume 66, pages 831–834 (2021)Cite this article

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Abstract

FGFR3 encodes a transmembrane receptor tyrosine kinase that has six autophosphorylation sites of tyrosine. Among them, Y770 is a negative regulatory site for the downstream signaling of FGFR3. Constitutive active mutations in FGFR3 are involved in human developmental disorders including familial acanthosis nigricans, an autosomal dominant disorder characterized by general hyperpigmentation with mild acanthosis of the epidermis. Here, we report two unrelated cases of familial acanthosis nigricans with a heterozygous c.2302G>T (p.E768*) mutation in FGFR3 (NM_000142.5). FGFR3 mRNA purified from the skin lesion neither showed aberrant splicing nor nonsense-mediated mRNA decay, indicating that the FGFR3 mutant simply lacked the C-terminal 768–806 amino acids including Y770. While all of the known pathogenic mutations were missense mutations in FGFR3 showing autosomal dominant trait, the c.2302G>T mutation of FGFR3 is a unique autosomal dominant nonsense mutation that causes familial acanthosis nigricans probably via loss of negative regulatory autophosphorylation site of FGFR3.

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Acknowledgements

The authors wish to thank the patients and patient’s family members for their kind collaboration.

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Authors and Affiliations

  1. Department of Dermatology, Keio University School of Medicine, Tokyo, Japan

    Umi Tahara, Satomi Aoki, Showbu Sato, Masayuki Amagai & Akiharu Kubo

  2. Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan

    Masahito Yasuda

  3. Department of Dermatology, Kakogawa Central City Hospital, Kakogawa, Japan

    Yozo Yamada

Authors
  1. Umi Tahara
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  2. Masahito Yasuda
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  3. Yozo Yamada
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  4. Satomi Aoki
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  5. Showbu Sato
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  6. Masayuki Amagai
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  7. Akiharu Kubo
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Correspondence to Akiharu Kubo.

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Tahara, U., Yasuda, M., Yamada, Y. et al. Autosomal dominant familial acanthosis nigricans caused by a C-terminal nonsense mutation of FGFR3. J Hum Genet 66, 831–834 (2021). https://doi.org/10.1038/s10038-021-00905-1

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  • DOI: https://doi.org/10.1038/s10038-021-00905-1

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