Novel compound heterozygous mutations in the PARK2 gene identified in a Chinese pedigree with early-onset Parkinson's disease

Objects: To capture point mutations and short insertions/deletions in 49 previously reported genes associated with Parkinson's disease (PD) in a Chinese pedigree with early-onset Parkinson's disease (EOPD)-affected individuals. Methods: Clinical examinations and genomic analysis were performed on 21 subjects belonging to three generations of a Chinese family. Target region capture and high-throughput sequencing were used for screening 49 genes, which were previously reported to be associated with PD. The direct Sanger sequencing method in all subjects further verified the abnormal DNA fragments in the PARK2 gene. Results: Four family members, including a mother (I-1) and her three children (II-2, II-3, and II-7), were diagnosed with PD by clinical manifestations and/or PET/CT imaging analyses. Novel compound heterozygous mutations, consisting of a fragment deletion in exon 1 to 2 (EX 1-2 del) and a splicing point mutation c.619-1 (G>C) in the 6th intron of the PARK2 gene, were identified in II-2, II-3, and II-7. Individual EX 1-2 del or c.619-1 (G>C) mutations were detected in I-1 and the third generation (III-2, 3, 5, 10, and 11).Other mutations were not detected in the 49 known PD-associated genes. Conclusion: Novel compound heterozygous mutations were identified in a Chinese pedigree and might represent a cause of familial EOPD with autosomal dominant inheritance.