Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients.
J Hum Genet
; 58(7): 455-60, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23739126
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
População Negra
/
Povo Asiático
/
Face
/
Síndromes de Imunodeficiência
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Animals
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão