Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients

Hirohisa Nitta, Motoko Unoki, Kenji Ichiyanagi, Tomoki Kosho, Tomonari Shigemura, Hiroshi Takahashi, Guillaume Velasco, Claire Francastel, Capucine Picard, Takeo Kubota, Hiroyuki Sasaki

    Research output: Contribution to journalArticle

    20 Citations (Scopus)

    Abstract

    Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that shows DNA hypomethylation at pericentromeric satellite-2 and -3 repeats in chromosomes 1, 9 and 16. ICF syndrome is classified into two groups: type 1 (ICF1) patients have mutations in the DNMT3B gene and about half of type 2 (ICF2) patients have mutations in the ZBTB24 gene. Besides satellite-2 and -3 repeats, α-satellite repeats are also hypomethylated in ICF2. In this study, we report three novel ZBTB24 mutations in ICF2. A Japanese patient was homozygous for a missense mutation (C383Y), and a Cape Verdean patient was compound heterozygous for a nonsense mutation (K263X) and a frame-shift mutation (C327W fsX54). In addition, the second Japanese patient was homozygous for a previously reported nonsense mutation (R320X). The C383Y mutation abolished a C2H2 motif in one of the eight zinc-finger domains, and the other three mutations caused a complete or large loss of the zinc-finger domains. Our immunofluorescence analysis revealed that mouse Zbtb24 proteins possessing a mutation corresponding to either C383Y or R320X are mislocalized from pericentrometic heterochromatin, suggesting the importance of the zinc-finger domains in proper intranuclear localization of this protein. We further revealed that the proper localization of wild-type Zbtb24 protein does not require DNA methylation.

    Original languageEnglish
    Pages (from-to)455-460
    Number of pages6
    JournalJournal of Human Genetics
    Volume58
    Issue number7
    DOIs
    Publication statusPublished - Jul 1 2013

    Fingerprint

    Mutation
    Zinc Fingers
    Nonsense Codon
    Chromosomes, Human, Pair 16
    Chromosomes, Human, Pair 9
    Frameshift Mutation
    Proteins
    Heterochromatin
    Chromosomes, Human, Pair 1
    Missense Mutation
    DNA Methylation
    Genes
    Fluorescent Antibody Technique
    DNA

    All Science Journal Classification (ASJC) codes

    • Genetics
    • Genetics(clinical)

    Cite this

    Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients. / Nitta, Hirohisa; Unoki, Motoko; Ichiyanagi, Kenji; Kosho, Tomoki; Shigemura, Tomonari; Takahashi, Hiroshi; Velasco, Guillaume; Francastel, Claire; Picard, Capucine; Kubota, Takeo; Sasaki, Hiroyuki.

    In: Journal of Human Genetics, Vol. 58, No. 7, 01.07.2013, p. 455-460.

    Research output: Contribution to journalArticle

    Nitta, H, Unoki, M, Ichiyanagi, K, Kosho, T, Shigemura, T, Takahashi, H, Velasco, G, Francastel, C, Picard, C, Kubota, T & Sasaki, H 2013, 'Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients', Journal of Human Genetics, vol. 58, no. 7, pp. 455-460. https://doi.org/10.1038/jhg.2013.56
    Nitta, Hirohisa ; Unoki, Motoko ; Ichiyanagi, Kenji ; Kosho, Tomoki ; Shigemura, Tomonari ; Takahashi, Hiroshi ; Velasco, Guillaume ; Francastel, Claire ; Picard, Capucine ; Kubota, Takeo ; Sasaki, Hiroyuki. / Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients. In: Journal of Human Genetics. 2013 ; Vol. 58, No. 7. pp. 455-460.
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    abstract = "Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that shows DNA hypomethylation at pericentromeric satellite-2 and -3 repeats in chromosomes 1, 9 and 16. ICF syndrome is classified into two groups: type 1 (ICF1) patients have mutations in the DNMT3B gene and about half of type 2 (ICF2) patients have mutations in the ZBTB24 gene. Besides satellite-2 and -3 repeats, α-satellite repeats are also hypomethylated in ICF2. In this study, we report three novel ZBTB24 mutations in ICF2. A Japanese patient was homozygous for a missense mutation (C383Y), and a Cape Verdean patient was compound heterozygous for a nonsense mutation (K263X) and a frame-shift mutation (C327W fsX54). In addition, the second Japanese patient was homozygous for a previously reported nonsense mutation (R320X). The C383Y mutation abolished a C2H2 motif in one of the eight zinc-finger domains, and the other three mutations caused a complete or large loss of the zinc-finger domains. Our immunofluorescence analysis revealed that mouse Zbtb24 proteins possessing a mutation corresponding to either C383Y or R320X are mislocalized from pericentrometic heterochromatin, suggesting the importance of the zinc-finger domains in proper intranuclear localization of this protein. We further revealed that the proper localization of wild-type Zbtb24 protein does not require DNA methylation.",
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    AU - Takahashi, Hiroshi

    AU - Velasco, Guillaume

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