[Genetic study of a Parkinson's disease pedigree caused by compound heterozygous mutations in PARK2 gene]
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Meihong Chen1, Zhidong Cen, You Chen
1Department of Neurology, Tiantai People's Hospital, Tiantai, Zhejiang 317200, China. luoweirock@zju.edu.cn.
Objective:
To explore the genetic basis for a Chinese pedigree where three siblings were affected with Parkinson's disease.
Methods:
Multiple ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) were employed to detect the causative mutation. Sanger sequencing of cDNA was also used for verify the effect of mutation on the transcription of RNA.
Results:
Heterozygous deletion of exon 3 of the PARK2 gene was detected by MLPA, while a heterozygous splice site variant c.619-3G>C was detected by NGS. Both mutations were shown to result in aberrant transcripts of the PARK2 gene (loss of exons 3 and 6, respectively) by Sanger sequencing of cDNA. Both mutations have co-segregated with the disease in the pedigree.
Conclusion:
Compound heterozygous mutations of the PARK2 gene probably underlie the disease in this pedigree. Identification of the splice site variant c.619-3G>C has expanded the mutation spectrum of the PARK2 gene.