Identification of a Premature Termination Mutation in the Proline-Rich Transmembrane Protein 2 Gene in a Chinese Family with Febrile Seizures.

Febrile seizures (FS), the most frequent type of seizures in children, occur in neurologically normal infants and children between the ages of 3 months and 5 years with genetic predisposition. The aim of this study was to identify the responsible gene in a four-generation Chinese Han pedigree with autosomal dominant FS. Seven family members (three affected and four unaffected) were enrolled in this study. Exome sequencing was conducted and a duplication mutation c.649dupC (p.R217Pfs*8) in the proline-rich transmembrane protein 2 gene (PRRT2) was identified. The mutation co-segregated with the disorder and was absent in normal controls. To our knowledge, this is the first report of a pedigree with complete penetrance of FS, which is caused by mutation in the PRRT2 gene. FS is a novel phenotype of the c.649dupC (p.R217Pfs*8) mutation. Our discovery broadens the spectrum of genetic causes of FS and the spectrum of phenotypes linked to mutation in the PRRT2 gene.