Identification of mutations in TET2 gene (4q24). (A) Genomic sequencing of all coding TET2 exons revealed the presence of nonsense, missense, and frameshift mutations. These mutations were homozygous and associated with UPD4q (top left), hemizygous associated with deletion (top right), or heterozygous associated with no chromosomal lesion (bottom right). Unique compound heterozygosity was found in 1 patient (bottom left). Detailed description of the SNP-A karyograms is provided in Figure 1B. (B) Schematic representation of the topographic distribution of the individual mutations in the TET2 protein (Isoform A NM_001127208). Amino acid sequences of TET family members are aligned (TET2, TET1, and TET3). *Highly conserved residues among all 3 proteins (LCXH domains). Most mutations were found in 2 conserved domains, LCXH 1 and 2 (50%, missense changes, frameshifts and codon stop changes are in red and underlined) while nonsense and frameshift mutations were more prominent in the N terminus (62%). Q1084P and Y867H are novel, unannotated SNPs (see “Note added in proof”).