Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome

Megumu Saito, Akihiro Fujisawa, Ryuta Nishikomori, Naotomo Kambe, Mami Nakata-Hizume, Momoko Yoshimoto, Katsuyuki Ohmori, Ikuo Okafuji, Takakazu Yoshioka, Takashi Kusunoki, Yoshiki Miyachi, Toshio Heike, Tatsutoshi Nakahata

Research output: Contribution to journalArticle

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Abstract

Chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is a severe inflammatory disease that was recently found to be associated with mutations in CIAS1. However, CIAS1 mutations have been detected in only half of CINCA syndrome patients, and it remains unclear which genes are responsible for the syndrome in the remaining patients. We describe here a patient with CINCA syndrome who exhibited CIAS1 somatic mosaicism. We genetically analyzed the CIAS1 gene in various blood cells and the buccal mucosa of the patient. The production of interleukin-1β (IL-1β) by peripheral blood mononuclear cells (PBMCs) was measured by enzyme-linked immunosorbent assay, and the ability of the mutant CIAS1 gene to enhance ASC-dependent NF-κB activation was assessed to confirm that the mutations of CIAS1 found were responsible for the patient's clinical manifestations of the CINCA syndrome. The patient had 1 heterologous single-nucleotide polymorphism, 587G >A (S196N), and 1 heterologous mutation, 1709A > G (Y570C), in exon 3 of CIAS1. The latter mutation was found to occur as somatic mosaicism. The patient's PBMCs produced a large amount of IL-1β in the absence of stimulation, unlike those from controls or from his mother, who also bore the S196N polymorphism. In addition, the Y570C mutation (with or without the S196N polymorphism) increased the ability of CIAS1 to induce ASC-dependent NF-κB activation, unlike the wild-type gene or the gene bearing the S196N polymorphism alone. The findings in this patient indicate that somatic mosaicism is one reason CIAS1 mutations have not been detected in some patients with CINCA syndrome.

Original languageEnglish (US)
Pages (from-to)3579-3585
Number of pages7
JournalArthritis and Rheumatism
Volume52
Issue number11
DOIs
StatePublished - Nov 2005
Externally publishedYes

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Cryopyrin-Associated Periodic Syndromes
Mosaicism
Mutation
Blood Cells
Aptitude
Genes
Interleukin-1
Mouth Mucosa
Single Nucleotide Polymorphism
Exons
Enzyme-Linked Immunosorbent Assay
Mothers

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Saito, M., Fujisawa, A., Nishikomori, R., Kambe, N., Nakata-Hizume, M., Yoshimoto, M., ... Nakahata, T. (2005). Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome. Arthritis and Rheumatism, 52(11), 3579-3585. https://doi.org/10.1002/art.21404

Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome. / Saito, Megumu; Fujisawa, Akihiro; Nishikomori, Ryuta; Kambe, Naotomo; Nakata-Hizume, Mami; Yoshimoto, Momoko; Ohmori, Katsuyuki; Okafuji, Ikuo; Yoshioka, Takakazu; Kusunoki, Takashi; Miyachi, Yoshiki; Heike, Toshio; Nakahata, Tatsutoshi.

In: Arthritis and Rheumatism, Vol. 52, No. 11, 11.2005, p. 3579-3585.

Research output: Contribution to journalArticle

Saito, M, Fujisawa, A, Nishikomori, R, Kambe, N, Nakata-Hizume, M, Yoshimoto, M, Ohmori, K, Okafuji, I, Yoshioka, T, Kusunoki, T, Miyachi, Y, Heike, T & Nakahata, T 2005, 'Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome', Arthritis and Rheumatism, vol. 52, no. 11, pp. 3579-3585. https://doi.org/10.1002/art.21404
Saito M, Fujisawa A, Nishikomori R, Kambe N, Nakata-Hizume M, Yoshimoto M et al. Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome. Arthritis and Rheumatism. 2005 Nov;52(11):3579-3585. https://doi.org/10.1002/art.21404
Saito, Megumu ; Fujisawa, Akihiro ; Nishikomori, Ryuta ; Kambe, Naotomo ; Nakata-Hizume, Mami ; Yoshimoto, Momoko ; Ohmori, Katsuyuki ; Okafuji, Ikuo ; Yoshioka, Takakazu ; Kusunoki, Takashi ; Miyachi, Yoshiki ; Heike, Toshio ; Nakahata, Tatsutoshi. / Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome. In: Arthritis and Rheumatism. 2005 ; Vol. 52, No. 11. pp. 3579-3585.
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