DNMT3B mutations and DNA methylation defect define two types of ICF syndrome

Hum Mutat. 2005 Jan;25(1):56-63. doi: 10.1002/humu.20113.

Abstract

ICF syndrome is a rare autosomal recessive disease characterized by variable immunodeficiency, centromeric instability, and facial abnormalities. Mutations in the catalytic domain of DNMT3B, a gene encoding a de novo DNA methyltransferase, have been recognized in a subset of patients. ICF syndrome is a genetic disease directly related to a genomic methylation defect that mainly affects classical satellites 2 and 3, both components of constitutive heterochromatin. The variable incidence of DNMT3B mutations and the differential methylation defect of alpha satellites allow the identification of two types of patients, both showing an undermethylation of classical satellite DNA. This classification illustrates the specificity of the methylation process and raises questions about the genetic heterogeneity of the ICF syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Centromere
  • Cohort Studies
  • Craniofacial Abnormalities / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methylation*
  • DNA Mutational Analysis
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Male
  • Mutation*
  • RNA Splicing
  • Sequence Analysis, DNA
  • Syndrome

Substances

  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3B