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Analysis of IKBKG/NEMO gene in five Japanese cases of incontinentia pigmenti with retinopathy: fine genomic assay of a rare male case with mosaicism

Journal of Human Genetics volume 66, pages 205–214 (2021)Cite this article

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A Correction to this article was published on 27 January 2021

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Abstract

Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis that is usually lethal in utero in males, though exceptionally they survive very rarely either with Klinefelter syndrome or a somatic mosaicism. We performed genomic analysis of five Japanese IP patients including a rare boy case, all of whom were definite cases with retinopathy. Four patients including the boy revealed the recurrent exon 4–10 deletion in the sole known causative gene IKBKG/NEMO, which was confirmed by various specific PCR techniques. The boy’s saliva DNA showed a mosaicism consisting of the deletion and intact alleles, but his blood DNA did not. Relative quantification analysis of the real-time PCR data by ∆∆CT method estimated the mosaicism ratio of the boy’s saliva as 45:55 (deletion:intact). A genomic analysis for the recurrent deletion at the nucleotide sequence level has been performed directly using patient’s DNA and it has been clarified that the breakpoints are within two MER67B repeats in the intron 3 and downstream of exon 10. This is the first report of the assay for the mosaicism ratio of a male IP case with a recurrent exon 4–10 deletion of IKBKG/NEMO and the sequencing analysis of the breakpoints of the recurrent deletion directly using patient’s sample.

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  • 27 January 2021

    A Correction to this paper has been published: https://doi.org/10.1038/s10038-021-00900-6

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Acknowledgements

Grants from the Initiative on Rare and Undiagnosed Diseases from the Japan Agency for Medical Research and Development (AMED) (no. JP18ek0109301 to YH), the Grants-in-Aid for Scientific Research grants (KAKENHI) from the Japan Society for the Promotion of Science (JSPS) (no. JP17K11447 to YH), and the HUSM Grant-in-Aid 2019 of Hamamatsu University School of Medicine supported this study.

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Authors and Affiliations

  1. Department of Photomedical Genomics, Institute of Medical Photonics Research, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Muhammad Nazmul Haque, Masafumi Ohtsubo, Kentaro Ohishi & Shinsei Minoshima

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

    Muhammad Nazmul Haque, Katsuhiro Hosono, Kentaro Kurata, Miho Sato & Yoshihiro Hotta

  3. Department of Ophthalmology and Laboratory for Visual Science, National Center for Child Health and Development, Tokyo, Japan

    Sachiko Nishina, Shiro Nakao & Noriyuki Azuma

  4. Department of Dermatology, National Center for Child Health and Development, Tokyo, Japan

    Kazue Yoshida

  5. Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan

    Maki Fukami

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  1. Muhammad Nazmul Haque
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Correspondence to Shinsei Minoshima.

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The authors declare that they have no conflict of interest.

Ethical approval

The Institutional Review Board of the National Center for Child Health and Development and the Ethics Committee of Hamamatsu University School of Medicine approved this study, which adhered to the tenets of the Declaration of Helsinki.

Informed consent

The parents of the current patients provided written informed assent for their children and informed consent for themselves regarding ophthalmic examinations and treatment under general anesthesia, genetic analysis and publication of this report. A healthy person included in this study as control also provided written informed consent for DNA analysis and publication.

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Haque, M.N., Ohtsubo, M., Nishina, S. et al. Analysis of IKBKG/NEMO gene in five Japanese cases of incontinentia pigmenti with retinopathy: fine genomic assay of a rare male case with mosaicism. J Hum Genet 66, 205–214 (2021). https://doi.org/10.1038/s10038-020-00836-3

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