Figure 4.

Homozygous DNMT3B mutation in ICF Family 2. Family 2 is a consanguineous Turkish kindred with an affected female proband (P3) described by Wijmenga et al. (8). In P3 of Family 2, a homozygous CpG to CpA transition (IVS21–11G → A) was detected 11 nucleotides upstream from the normal 5′ splice acceptor site for exon 22 in the mt3b-23f:23r PCR product. The mutation can be detected by HpaII analysis of the product; normal alleles are digested by HpaII, but the mutant one is not. The father (F2) and mother (M2) of P3 are both heterozygous for the mutation and the two unaffected daughters homozygous for normal alleles. The mutation creates an AG dinucleotide that is predicted to create a new splice acceptor site that retains nine intronic nucleotides at the 5′ end of exon 22.