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WWOX

Gene product: WW Domain-Containing Oxidoreductase.

Protein function: It is highly expressed in cerebral cortical neurons and hippocampus, and plays a key role in neuronal development, differentiation and protection. Its loss of function can lead to abnormal neuronal excitation, neuronal damage and neurodegeneration, involving mitochondrial dysfunction and cell apoptosis [1].

Phenotype: Developmental and epileptic encephalopathy 28 (AR) (some may present as Infantile Epileptic Spasms Syndrome and Epilepsy Of Infancy With Migrating Focal Seizures) [2, 4]; spinocerebellar ataxia (AR) [3].

Mutation database: ClinVar。

Clinical research: PubMed (PMID: 36779245 (Epilepsia . 2023))

Medication reminder: The medication is mainly selected according to the epilepsy syndrome, which is often refractory to anti-epileptic drugs. Some patients have a certain effect on the ketogenic diet (there are also some reports of poor treatment effects). There are also 2 case reports that epilepsy was controlled for more than 2 years after the use of sodium valproate combined with levetiracetam [5-7].

 

References:

  1. The WWOX gene in brain development and patholog. Exp Biol Med (Maywood). 2020 Jul;245(13):1122-1129.
  2. The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration. Orphanet J Rare Dis. 2014 Jan 23:9:12.
  3. A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23. Brain. 2007 Jul;130(Pt 7):1921-8.
  4. WWOX developmental and epileptic encephalopathy: Understanding the epileptology and the mortality risk. Epilepsia . 2023 May;64(5):1351-1367.
  5. Epilepsy in patients with WWOX-related epileptic encephalopathy (WOREE) syndrome. Epileptic Disord. 2022 Aug 1;24(4):697-712.
  6. Expansion of the clinical and molecular spectrum of WWOX-related epileptic encephalopathy. Am J Med Genet A. 2023 Mar;191(3):776-785.
  7. 王婷，程苗苗，刘文玮,等. WWOX基因相关发育性癫痫性脑病患儿基因型及临床表型特点. 中华儿科杂志，2024，62(08):752-757.