All TPFS patients reported so far have had changes at a single amino acid (at position 65) of the PCGF2 protein. PCGF2 mutations will be detected by DNA sequencing (single gene, multi-gene panel, exome or whole genome sequencing).
Further research is required to understand why PCGF2 mutations cause disease. PCGF2 works with other proteins to control a network of genes involved in the development of the body. It is suspected that the mutations reduce the ability of PCGF2 to work properly, therefore disrupting the network. This leads to the effects seen on the heart, brain, skeleton and face.