PEHO syndrome is caused by variants in the coiled-coil domain-containing protein 88A gene.
A homozygous frameshift deletion in CCDC88A (c.2313delT, p.Leu772*ter) has been reported. This variant produced a truncated protein lacking the crucial C-terminal half of CCDC88A (Girdin). In addition, homozygous nonsense mutation in CCDC88A (c.1292G > A, p.Trp431*stop gain) has been reported. This variant resulted in a complete loss of protein function due to premature stop gain. Whole exome sequencing identified the variants in the two families reported. The variants were confirmed by Sanger sequencing.
Mice studies suggested loss of CCDC88A is a cause of the PEHO/ PEHO-like phenotype.