The Value of Chromosome Analysis to Interrogate Variants in DNMT3B Causing Immunodeficiency, Centromeric Instability, and Facial Anomaly Syndrome Type I (ICF1)
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Immunodeficiency, centromeric instability, facial anomalies syndrome (ICF) is a rare autosomal recessive disorder and is one of the few heritable human diseases caused by mutations in a DNA methyltransferase . The majority of patients with ICF syndrome have a defect in either the DNMT3B or ZBTB24 gene, classified as ICF1 and ICF2, respectively . DNMT3B, in conjunction with DNMT3A and the catalytically inactive stimulatory factor DNMT3L, is responsible for de novo DNA methylation during embryogenesis and early development . DNMT3A and DNMT3B are responsible for methylating unique genomic targets, with DNMT3B being solely responsible for methylating cytosine residues of CpG dinucleotides in highly repetitive satellite 2 and 3 DNA of pericentromeric heterochromatin . Patients with biallelic pathogenic variants in DNMT3Bshow hypomethylation and characteristic aberrations of the pericentromeric regions of chromosomes 1, 9, and 16 in mitogen-stimulated...
This work was supported by The Jeffrey Modell Foundation (salary support for ESK).
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Conflict of Interest
The authors declare that they have no conflict of interest.
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