History of WWOX
The WWOX gene was first cloned in 2000 after researchers observed that deletions within the WWOX coding sequence were observed in up to 80% of breast cancer cases. Gene cloning is the process in which a gene of interest is located and copied (cloned) out of DNA extracted from an organism which allows for easier and more focused study of the gene’s function. It became clear that WWOX had a function as a tumour suppressor gene, or antioncogene. This function was largely attributed to WWOX’s WW domains, known to mediate protein-protein interaction. Several WWOX partners were identified and helped to define WWOX functions in health and disease.
The focus on WWOX’s role in cancer remains of interest to this day, but researchers also became aware of the important role WWOX plays in the regulation of a wide variety of other cellular functions, most notably the effect of WWOX deficiency on brain function. In 2006, WWOX researchers first noticed that WWOX was expressed in neuronal cells and in 2007 the first paper emerged which described a new childhood onset recessive spinocerebellar ataxia, epilepsy and mental retardation syndrome. The syndrome was named SCAR12 which is an abbreviation of spinocerebellar ataxia autosomal recessive 12. The disease affected children from a large consanguineous family and the defective gene was eventually confirmed as WWOX following whole exome sequencing conducted in 2014.
Not long after, many more reports implicating WWOX with severe early onsite epileptic encephalopathy started to emerge which lead to the classification of a more severe syndrome called EIEE28 also known as WOREE syndrome (WWOX-related epileptic encephalopathy).
The following articles are scientific in nature, but provide a good starting point for parents and physicians who are seeking a more in-depth understanding of WWOX related disorders and the underlying pathophysiology.
Parents Support Group
This Facebook group is a wonderful resource for parents of children suffering from WWOX related syndromes.