Abstract
BACKGROUND Mutations in the SYNJ1 gene have been associated with early-onset of atypical Parkinson's disease or severe neurodegeneration with intractable seizures. Due to the rarity of the disease, there were limitations in the quality of available treatment options for SYNJ1-related diseases. METHODS Two affected siblings from a non-consanguineous family were evaluated through a set of clinical and laboratory tests. The genetic screening was performed through exome next generation sequencing. SYNJ1 mutant transcripts were purified and cloned into the vectors for Sanger sequence of single-stranded DNA. Relative level of the SYNJ1 transcript was measured by quantitative PCR. RESULTS The clinical features were characterized by a triad of symptomatic progression including diplopia, dystonia, and Parkinsonism. The dystonic symptoms were outstanding in the siblings, which preceded the Parkinsonism symptoms and became the main symptoms. Clonazepam resolved the clinical symptoms, especially the severe trunk dystonia and dystonic postures of limbs. Compound heterozygous variants (c.2579-2A > G; p.A860Gfs*5 and c.3845C > A; p.P1282L) were identified in the SYNJ1 gene co-segregating in this family. The proline residue is highly conserved across species and predicted to be damaging by several in silico tools. The splice site variant caused a skip of exon 20 and a significant reduction of the SYNJ1 transcript expression. CONCLUSIONS Our study expanded the clinical and genetic spectrums of the SYNJ1-related diseases. Although our study was a preliminary observation, it indicated that clonazepam could improve the dystonic symptoms caused by mutations in the SYNJ1 gene.
