The Value of Novel Candidate Gene Analysis in Individuals with Epilepsy undergoing Exome Sequencing
Since 2011, clinical diagnostic exome sequencing (DES) has proven instrumental in providing molecular diagnoses for patients with wide-ranging, previously undiagnosed genetic diseases.
Studies continue to highlight the usefulness of DES, particularly in patients with epilepsy, to yield a high diagnostic rate and to impact both genetic counseling and treatment 1,2.
Novel candidate genes for patients with epilepsy continue to be elucidated3.
Herein, we report novel candidate gene findings and clinical characteristics of an unselected laboratory cohort of patients with epilepsy.
In our cohort, potentially relevant novel candidate genes were identified in 35/396 (8.8%) of non-characterized cases.
Of these patients, two-thirds appeared to have an epileptic encephalopathy, which suggests that analysis and reporting of novel genetic etiologies may be particularly useful for this patient population.
Of these 24 patients, 16 (66.7%) had electroclinical features consistent with an epileptic encephalopathy.
Of the reported novel candidate genes, 9/35 (25.7%) were subsequently re-classified to characterized gene findings due to newly published literature, including PURA, SON, and ZBTB18. due to additional reported patients in independent peer-reviewed literature, indicating that systematic analysis of novel genetic etiologies according to established reporting criteria has clinical validity and can be applied on a diagnostic basis.