Progressive
encephalopathy,
edema,
hypsarrhythmia, and
optic atrophy (
PEHO) syndrome is an unusual Mendelian phenotype of unidentified origin that causes profound
intellectual disability, optic nerve/cerebellar
atrophy, epileptic
seizures, developmental progress, pedal
edema, and early death. Uncharacteristic affected individuals are often classified as having
PEHO-like syndrome, although they may be misdiagnosed as having epileptic
encephalopathy, a potential result of early birth. In this study, we report a consanguineous Saudi family with a novel homozygous
nonsense mutation of the CCDC88A gene causing
PEHO-like syndrome. The children were suffering from developmental delay,
epilepsy, mental disability, optic nerve/cerebellar
atrophy, and pedal
edema. Whole exome sequencing was conducted for the members of the family who have the disorder to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation, identified a novel homozygous
nonsense mutation c. 1292G > A, which was caused by p.Trp431* stop gain. This mutation was ruled out in 100 unrelated healthy controls. The nonsense homozygous mutation detected in this study has not yet been reported as pathogenic in the literature or various databases. In conclusion, a complete loss of
protein function due to premature stop gain was caused by a mutation in exon 12 of CCDC88A. This loss may lead to PEHO phenotype. CCDC88A gene may therefore play an important and critical role for multiple aspects of normal human neurodevelopment.