Genetic study of a Chinese pedigree with early onset Parkinson's disease caused by novel compound heterozygous mutations in PARKIN gene

Objective: To explore the genetic basis for a Chinese pedigree where two siblings were affected with early-onset Parkinson's disease (EOPD).

Methods: Clinical examinations and genomic analyses were performed on five subjects belonging to two generations of a Han Chinese family. Target regions capture and high throughput sequencing were used to screen these genes associated with Parkinson's disease (PD), tremor, spinocerebellar ataxia, and dystonia. The multiplex ligation dependent probe amplification (MLPA) method was applied to detect rearrangements and large deletion in PARKIN exons.

Results: Two family members were diagnosed with PD by clinical manifestations. Compound heterozygous mutations, consisting of a fragment deletion in exon 2 and 3 of the PARKIN gene, identified by MLPA in II-3, II-5. Individual exon2 deletion mutations were detected in II-1 while individual exon3 deletion mutations were detected in two thirds generations (III-5, III-6). The compound heterozygous mutations have co-segregated with the disease in the pedigree. Other mutations in some genes associated with PD, tremor, dystonia and other movement disorders were not detected.

Conclusion: A novel compound heterozygous deletion mutations of the PARKIN gene were identified in a Chinese pedigree and might represent a cause of familial EOPD with autosomal dominant inheritance. Early-onset Parkinson's disease (PD) with PARKIN gene mutation has genetic and clinical heterogeneity.