Mutations in the WWOX gene have been reported in a number of patients with various neurological disorders including spino-cerebellar ataxia, intellectual disability, epilepsy, and epileptic encephalopathy.
We provide the first detailed description of patients harboring a splice-site variant in the WWOX gene and propose that the clinical synopsis of WWOX related epileptic encephalopathy should be broadened to include facial dysmorphism.
This additional family confirms the genotype-phenotype correlation with WWOX-null alleles associated with the most severe form of WWOX-related epileptic encephalopathy with premature death.
A novel missense variant in the SDR domain of the WWOX gene leads to complete loss of WWOX protein with early-onset epileptic encephalopathy and severe developmental delay.
WWOX-related epileptic encephalopathy is a rare condition but it should be considered in cases having early epileptic spasms and parental consanguinity.
Further, clinical symptoms associated with WDR45 mutations ranged from early-onset epileptic encephalopathy in a male patient with a deletion of WDR45 to only mild cognitive delay in a female patient, suggesting that analysis of this gene should be considered more often in patients with developmental delay, regardless of severity.
Using whole-genome sequencing technique, compound heterozygous mutations of the VARS2 gene were revealed, with one previously unreported frameshift mutation.<b>Conclusion:</b> Our report extends the phenotypic spectrum of VARS2-related disorders with an initial presentation of epileptic encephalopathy and early death due to malignant arrhythmia.
USP9X mutations were identified by resequencing a cohort of patients with epileptic encephalopathy, one patient harbored a de novo missense mutation and another a novel coding mutation.
Mutations in the Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) gene are associated with a range of inherited neurological disorders, from drug-refractory lethal epileptic encephalopathy and DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, seizures) to non-syndromic hearing loss.
Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.
To our knowledge, this is the first description of mutations in UBA5 since the initial discovery that pathogenic biallelic variants in the gene cause early-onset epileptic encephalopathy.