Two siblings with immunodeficiency, facial abnormalities and chromosomal instability without mutation in DNMT3B gene but liability towards malignancy; a new chromatin disorder delineation?

• Published in: Molecular Cytogenetics 2010, Vol.3, p.5
• Main Authors: Polityko, Anna, Khurs, Olga, Rumyantseva, Natalia, Naumchik, Irina, Kosyakova, Nadezda, Tönnies, Holger, Sperling, Karl, Neitzel, Heidemarie, Weise, Anja, Liehr, Thomas
• Format: Report
• Language: English
• Subjects: Chromatin; Gene mutations; Health aspects; Methyltransferases
• ISSN: 1755-8166; 1755-8166
• DOI: 10.1186/1755-8166-3-5

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. 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. 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'.