Open AccessNovel compound heterozygous mutations in the PARK 2 gene identified in a Chinese pedigree with early‐onset Parkinson's disease
Author(s) -
Shi Yingying,
Kawakami Hideshi,
Zang Weizhou,
Li Gang,
Zhang Jiewen,
Xu Changshui
Publication year - 2018
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.901
Subject(s) - compound heterozygosity , sanger sequencing , genetics , exon , gene , biology , mutation , point mutation , genomic dna , intron , gene mutation , microbiology and biotechnology
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 PARK 2 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 PARK 2 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.