W44X mutation in the WWOX gene causes intractable seizures and developmental delay: a case report.

Loai Elsaadany,Tawfeg Ben-Omran,Mahmoud El-Said,Hussein Kamel,Rehab Ali

doi:10.1186/s12881-016-0317-z

Abstract

BackgroundWW domain containing oxidoreductase (WWOX) gene was cloned in 2000; alteration has been seen in many cancer cells. It acts as a tumor suppresser by blocking cell growth and causing apoptosis. WWOX protein showed different expression of mice brain and spinal cord, for which deletion causes seizure and early death.Case presentationClinical and molecular characteristics of a consanguineous family show a homozygous mutation of WWOX gene at specific bases, causing a debilitating syndrome characterized by growth retardation, intractable epilepsy, intellectual disability, and early death.Using Whole Exome Sequencing (WES), a novel homozygous mutation in the WWOX gene is identified in a consanguineous Arab family from Qatar with two daughters who presented with intractable seizure and developmental delay.ConclusionThe study presents the importance of human WWOX gene for brain development and the association between gene mutation and epileptic encephalopathy. It also highlights the power of WES particularly in clinically challenging cases.

Highlights

WW domain containing oxidoreductase (WWOX) gene was cloned in 2000; alteration has been seen in many cancer cells
The study presents the importance of human WWOX gene for brain development and the association between gene mutation and epileptic encephalopathy
This study identifies two siblings with novel WWOX gene mutation who presented for evaluation of epileptic encephalopathy

Summary

Conclusion

This family exemplifies the challenges in establishing an accurate diagnosis in patients presented with nonspecific epileptic encephalopathy and we recommend performing WES as a first line test to reach the final diagnosis in populations with high rates of consanguinity. The role of WWOX gene in brain development is crucial and the relationship between epileptic encephalopathy with gene mutation warrant further studies to determine the exact pathophysiology.

Background

Discussion