A novel FBXO7-R345P mutation in a Chinese family with autosomal recessive parkinsonian-pyramidal syndrome.

Background: Mutations in the F-box protein 7 (FBXO7) gene is one of the genetic causes of early-onset Parkinson's disease, which usually presents as autosomal recessive early-onset parkinsonian-pyramidal syndrome (PPS). Herein, we report a Chinese PPS family with a novel FBXO7 homozygous mutation.

Methods: Clinical data of the proband and his affected sister manifesting as early-onset parkinsonism combined with pyramidal signs were collected. DNAs of the two affected siblings, an unaffected sibling and their unaffected mother were isolated. Whole-exome sequencing (WES) was performed for the proband. After bioinformatic analysis, targeted variants were validated by Sanger sequencing in the family members available for DNAs.

Results: The proband began to walk unsteadily at 30-year-old and developed mild parkinsonism and stiffness in both lower extremities 4 years later. His older sister also manifested as early-onset parkinsonism with stiffness in both lower limbs and postural instability. Both the proband and his older sister carried a novel homozygous FBXO7 mutation in exon 7 (c.1034G > C, p. R345P). The homozygous mutation co-segregated with disease in this pedigree. The mutation located at a highly conserved amino acid residue in the F-box domain, which was predicted to be damaging in silico.

Conclusions: Our study expands the mutational spectrum of autosomal recessive early-onset Parkinson's disease (PARK15) caused by FBXO7 mutations.