Abstract
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.
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Acknowledgments
The authors also, acknowledge with thanks Science and Technology Unit, King Abdul-Aziz University for technical support.
Funding
This project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH)—King Abdul-Aziz City for Science and Technology—the Kingdom of Saudi Arabia—award number (12-BIO3059-03).
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M. I. N. conceived and designed the project. M. I. N. and A. A. A. performed experiments and confirmed these results. M. I. N., M. A. J., and A. G. C. analyzed and interpreted the data. M. I. N. and M. A. J. provided and interpreted phenotypic details for the patients. M. H. A., A. G. C., and K. O. A. advised on the study design and writing of the manuscript. M. I. N wrote the manuscript.
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Abdulkareem, A.A., Abulnaja, K.O., Jan, M.M. et al. A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family. Neurol Sci 40, 299–303 (2019). https://doi.org/10.1007/s10072-018-3626-5
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DOI: https://doi.org/10.1007/s10072-018-3626-5