Characterization of SNCA Multiplication in Parkinson's Disease: 2 New Cases and Evaluation of the Literature

• Published in: Movement disorders clinical practice (Hoboken, N.J.) Vol. 10; no. 10; pp. 1536 - 1541
• Main Authors: Duan, Ruo-Nan, Liu, Gui-Yu, Han, Yin-Lian, Li, Pei-Zheng, Zhang, Bo-Han, Liu, Yi-Ming
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2023; John Wiley & Sons, Inc
• Subjects: Case Series with Literature Review; Genetic counseling; Parkinson's disease; genotype–phenotype; Parkinson's disease; copy number variation; SNCA
• ISSN: 2330-1619; 2330-1619
• DOI: 10.1002/mdc3.13852

Alpha-synuclein ( ) copy number variations (CNV) have been certified as a causative mutation in patients with familial and sporadic Parkinson's disease (PD). We report three duplication cases diagnosed as PD. Through whole-exome sequencing, we identified a de novo 4.56 Mb repeated region in one patient and a 2.50 Mb repeated region in familial PD with two patients. In review of previous cases, we suggest that aggressive behavior is more remarkable in CNV4 patients. Meanwhile, frequency of cognition decline and dementia were slightly increased in CNV4 patients. We also illustrate a younger onset age in offspring than parent in familial multiplication PD cases. No difference was observed in disease duration between parent and offspring generation. Our findings demonstrated the clinical and genetic characteristics in PD with multiplication and provided strong evidence for genetic anticipation. These results may be instructive for future disease diagnosis and genetic counseling.