| RRC ID |
61102
|
| 著者 |
Nitta H, Unoki M, Ichiyanagi K, Kosho T, Shigemura T, Takahashi H, Velasco G, Francastel C, Picard C, Kubota T, Sasaki H.
|
| タイトル |
Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients.
|
| ジャーナル |
J Hum Genet
|
| 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.
|
| 巻・号 |
58(7)
|
| ページ |
455-60
|
| 公開日 |
2013-7-1
|
| DOI |
10.1038/jhg.2013.56
|
| PII |
jhg201356
|
| PMID |
23739126
|
| MeSH |
Adolescent
Adult
Animals
Asian People / genetics*
Black People / genetics*
Cell Line
Centromere / metabolism
Child, Preschool
Chromosome Aberrations
Chromosomes, Human, Pair 1 / genetics
Chromosomes, Human, Pair 1 / metabolism
Chromosomes, Human, Pair 16 / genetics
Cloning, Molecular
DNA Methylation
Face / abnormalities*
Female
Genomics
Humans
Immunologic Deficiency Syndromes / diagnosis
Immunologic Deficiency Syndromes / genetics*
Male
Mice
Mutation
NIH 3T3 Cells
Primary Immunodeficiency Diseases
Recombinant Fusion Proteins / genetics
Repressor Proteins / genetics*
Sequence Analysis
Zinc Fingers / genetics
|
| IF |
2.831
|
| リソース情報 |
| 遺伝子材料 |
EGFP-ZBTB24 WT (mouse) (RDB18170)
EGFP-ZBTB24 WT (human) (RDB18184) |
