Figure 3.

Homozygous DNMT3B mutation in ICF Family 1. Family 1 is a consanguineous Dutch kindred with two affected brothers (P1 and P2) that was described previously (8, 40). (A) A homozygous T to G transversion in codon 726 (2177T → G) was detected in the cDNA of P1 (mt3b-14f:15r product) that changes valine to glycine. (B) An assay was developed to rapidly screen human populations for this mutation. Digestion of the 3bx19 gt-f:mt3b-20r PCR product with EcoNI only occurs with the mutant allele, as seen for Family 1 members in which the father (F1) and mother (M1) are heterozygous and the two affected children (P1 and P2) are homozygous for the mutation (DNAs were derived from blood cells, except P1-LB, which is from a lymphoblastoid cell line used in screening cDNA for mutations; nrml is a normal control).