Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients
Authors:
- Motoko UnokiMotoko Unoki
- Kenji IchiyanagiKIKenji Ichiyanagi
- Tomoki KoshoTKTomoki Kosho
- Tomonari ShigemuraTSTomonari Shigemura
- Hiroshi TakahashiHTHiroshi Takahashi
- Guillaume VelascoGVGuillaume Velasco
- Claire FrancastelCFClaire Francastel
- Capucine PicardCPCapucine Picard
- Takeo KubotaTKTakeo Kubota
- Hiroyuki SasakiHSHiroyuki Sasaki
- 6 June 2013
- journal article
- research article
- Published by Springer Nature in Journal of Human Genetics
- Vol. 58 (7) , 455-460
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.Keywords
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