Molecular characteristics

The mutation identified is homozygous missense in the PIGF gene (NM_173074.3) in a predicted transmembrane domain. Both patients had the c.515C>G (p.Pro172Arg) variant, which may affect the structure of the PIGF, possibly affecting the amino acids incorporated in the membrane. Flow cytometry and functional analysis experiments showed a decrease in GPI-anchored proteins (GPI-APs) and a low-residual activity of PIGF despite normal protein levels, suggesting an effect of the mutations on protein activity rather than protein stability. Approximately one in every 200 mammalian proteins is a GPI-Aps. These proteins are important for neurological development and function, embryogenesis, immune response and signal transduction.