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Journal of Clinical Immunology

, Volume 39, Issue 8, pp 857–859 | Cite as

The Value of Chromosome Analysis to Interrogate Variants in DNMT3B Causing Immunodeficiency, Centromeric Instability, and Facial Anomaly Syndrome Type I (ICF1)

  • Erinn S. KellnerEmail author
  • Pamela A. Rathbun
  • Gary S. Marshall
  • Leandra K. Tolusso
  • Teresa A. Smolarek
  • Miao Sun
  • Sharat Chandra
  • Jack Bleesing
  • Rebecca A. Marsh
Letter to Editor
  • 40 Downloads

To the Editor:

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 [1]. The majority of patients with ICF syndrome have a defect in either the DNMT3B or ZBTB24 gene, classified as ICF1 and ICF2, respectively [2]. DNMT3B, in conjunction with DNMT3A and the catalytically inactive stimulatory factor DNMT3L, is responsible for de novo DNA methylation during embryogenesis and early development [3]. 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 [3]. Patients with biallelic pathogenic variants in DNMT3Bshow hypomethylation and characteristic aberrations of the pericentromeric regions of chromosomes 1, 9, and 16 in mitogen-stimulated...

Notes

Funding Information

This work was supported by The Jeffrey Modell Foundation (salary support for ESK).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10875_2019_704_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 17 kb)

References

  1. 1.
    Ehrlich M, Sanchez C, Shao C, Nishiyama R, Kehrl J, Kuick R, et al. ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation. Autoimmun. 2008;41(4):253–71.  https://doi.org/10.1080/08916930802024202.CrossRefGoogle Scholar
  2. 2.
    Weemaes CM, van Tol MJ, Wang J, van Ostaijen-ten Dam MM, van Eggermond MC, Thijssen PE, et al. Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects. Eur J Hum Genet. 2013;21(11):1219–25.  https://doi.org/10.1038/ejhg.2013.40.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Moarefi AH, Chedin F. ICF syndrome mutations cause a broad spectrum of biochemical defects in DNMT3B-mediated de novo DNA methylation. J Mol Biol. 2011;409(5):758–72.  https://doi.org/10.1016/j.jmb.2011.04.050.CrossRefPubMedGoogle Scholar
  4. 4.
    Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, et al. The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1999;96(25):14412–7.  https://doi.org/10.1073/pnas.96.25.14412.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Xu GL, Bestor TH, Bourc’his D, Hsieh CL, Tommerup N, Bugge M, et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature. 1999;402(6758):187–91.  https://doi.org/10.1038/46052.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Erinn S. Kellner
    • 1
    Email author
  • Pamela A. Rathbun
    • 2
  • Gary S. Marshall
    • 3
  • Leandra K. Tolusso
    • 2
  • Teresa A. Smolarek
    • 2
    • 4
  • Miao Sun
    • 2
    • 4
  • Sharat Chandra
    • 1
    • 4
  • Jack Bleesing
    • 1
    • 4
  • Rebecca A. Marsh
    • 1
    • 4
  1. 1.Division of Bone Marrow Transplantation and Immune DeficiencyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Division of Human GeneticsCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Division of Pediatric Infectious DiseasesUniversity of Louisville School of MedicineLouisvilleUSA
  4. 4.Department of PediatricsUniversity of CincinnatiCincinnatiUSA

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