Novel compound heterozygous mutations in the PARK2 gene identified in a Chinese pedigree with early‐onset Parkinson's disease. Issue 1 (19th December 2017) - Shi, Yingying
Abstract: 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. Abstract : There are about 49 genes associated with Parkinson's disease (PD), especially with early‐onset Parkinson's disease (EOPD), were previously reported. This study was designed to search point mutations and short insertions/deletions in these 49 reported genes in a Chinese pedigree with EOPD affected individuals. We found that several heterozygous mutations in this Chinese pedigree and parkin gene mutations might represent a cause of familial EOPD with autosomal dominant inheritance.