Research
Two siblings with immunodeficiency, facial abnormalities and chromosomal instability without mutation in DNMT3B gene but liability towards malignancy; a new chromatin disorder delineation?
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* Corresponding author: Anna Polityko polityko@yahoo.com
1 National Medical Center "Mother and Child", Orlovska Street 66, 220053 Minsk, Republic of Belarus
2 Jena University Hospital, Institute of Human Genetics and Anthropology, Kollegiengasse 10, D-07743 Jena, Germany
3 Institute of Human Genetics, Charité, Humboldt-University, Augustenburger Platz 1, 13353 Berlin, Germany
4 Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany
Molecular Cytogenetics 2010, 3:5 doi:10.1186/1755-8166-3-5
Published: 8 March 2010Abstract
Background
ICF syndrome (standing for Immunodeficiency, Centromere instability and Facial anomalies syndrome) is a very rare autosomal recessive immune disorder caused by mutations of the gene de novo DNA-methyltransferase 3B (DNMT3B). However, in the literature similar clinical cases without such mutations are reported, as well.
Results
We report on a family in which the unrelated spouses had two female siblings sharing similar phenotypic features resembling ICF-syndrome, i.e. congenital abnormalities, immunodeficiency, developmental delay and high level of chromosomal instability, including high frequency of centromeric/pericentromeric rearrangements and breaks, chromosomal fragments despiralization or pulverization. However, mutations in DNMT3B could not be detected.
Conclusion
The discovery of a new so-called 'chromatin disorder' is suggested. Clinical, molecular genetic and cytogenetic characteristics are reported and compared to other 'chromatin disorders'.