Whole exome sequencing reveals novel NOV and DCAF13 variants in a Chinese pedigree with familial cortical myoclonic tremor with epilepsy

Abstract Objective We report a large new family of familial cortical myoclonic tremor with epilepsy(FCMTE) from China and identify the possible causative gene(s) for the family. Method Whole exome sequencing of blood genomic DNA from 4 patients and 2 unaffected family members were performed. Detected variants and their cosegregation were confirmed by Sanger sequencing. Results We identified c.20 G > C variant in the DCAF13 gene and c.983 T > C variant in the NOV gene cosegregating in the family. There was no additional cross-over in the family to narrow to one gene. The two DCAF13 and NOV gene variants are located on 8q23.3 and 8q24.12, which is consistent with the location 8q23.3–q24.13 reported previously for a group of Japanese families. The DCAF13 variant is located in alternative transcription start site(TSS) and the function of alternative TSS is unknown. The missense NOV variant is near the C terminus in a site that is highly conserved across species. It was predicted to be deleterious on protein function. Conclusions In this study, we identify two novel variants in the DCAF13 and NOV genes associated with FCMTE in Asian populations. The interval between two variants is 15.6Mb, which is very close to each other. Future studies of additional families with this phenotype are warranted to confirm whether it is rare bigenic or monogenic inheritance.