Novel homozygous mutation in the WWOX gene causes seizures and global developmental delay: Report and review
| Autor: | Majed J. Al-Bu Ali, Salleh N. Ehaideb, Majid Alfadhel, Jaafer J. Al-obaid, Kareemah M. Aljassim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
WWOX Proband Microcephaly Neurosciences. Biological psychiatry. Neuropsychiatry Biology 03 medical and health sciences Epilepsy 0302 clinical medicine medicine cancer Global developmental delay wwox tumor suppressor gene oxidoreductase Exome sequencing Genetics General Neuroscience Chromosomal fragile site medicine.disease encephalopathy ww domain 030104 developmental biology Spinocerebellar ataxia epilepsy 030217 neurology & neurosurgery Regular Articles RC321-571 |
| Zdroj: | Translational Neuroscience, Vol 9, Iss 1, Pp 203-208 (2018) Translational Neuroscience |
| ISSN: | 2081-6936 |
| Popis: | TheWWOXgene has a WW domain containing oxidoreductase, which is located at the common fragile site FRA16D at chromosome 16q23.WWOXis a tumor suppressor gene that has been associated with several types of cancer such as hepatic, breast, lung, prostate, gastric, and ovarian. Recently WWOX has been implicated in epilepsy, where studies show homozygous loss-of-function mutation lead to early-infantile epileptic encephalopathy, spinocerebellar ataxia, intractable seizures and developmental delay, and early lethal microcephaly syndrome with epilepsy. Here we investigate two consanguineous Saudi families and we identified three probands with epileptic encephalopathy. Whole exome sequencing revealed a novel homozygous mutation in theWWOXgene in one proband. In addition, we identified a previously reportedWWOXmutation in two probands. Later on these findings were confirmed with Sanger sequencing. The underlying mechanism on how WWOX mutations lead to seizure remains elusive. To date very fewWWOXmutations have been associated with neurological disorder and our newly identified mutations support the notion that WWOX play an important role in neurons and will aid in better diagnosis and genetic counseling. |
| Databáze: | OpenAIRE |
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