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Review
. 2023 Aug 18;10(10):1536-1541.
doi: 10.1002/mdc3.13852. eCollection 2023 Oct.

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

Ruo-Nan Duan  1 , Gui-Yu Liu  2 , Yin-Lian Han  1 , Pei-Zheng Li  1 , Bo-Han Zhang  1 , Yi-Ming Liu  1
Affiliations
Review

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

Ruo-Nan Duan et al. Mov Disord Clin Pract. .

Abstract

Background: Alpha-synuclein (SNCA) copy number variations (CNV) have been certified as a causative mutation in patients with familial and sporadic Parkinson's disease (PD).

Case: We report three SNCA 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.

Literature review: 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 SNCA multiplication PD cases. No difference was observed in disease duration between parent and offspring generation.

Conclusions: Our findings demonstrated the clinical and genetic characteristics in PD with SNCA multiplication and provided strong evidence for genetic anticipation. These results may be instructive for future disease diagnosis and genetic counseling.

Keywords: Parkinson's disease; SNCA; copy number variation; genotype–phenotype.

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Figures

Figure 1
Figure 1
Genetic information of SNCA duplication patients and genotype–phenotype correlation of SNCA multiplication patients. Genogram of proband 1 (A) and proband 2 (B). Arrow indicates the proband. Black color indicates affected individuals. Whole‐exome sequencing identified multiplication in chromosome 4 in proband 1 (C) and proband 2 (D). (E) A genome review of SNCA duplication in proband 1. (F) A genome review of SNCA duplication in proband 2. MLPA results of proband 1 (G) and proband 2 (H). (I) Paired comparison of onset ages between parents and offspring revealed genetic anticipation. (J) Survival curve of disease duration in parents and offspring. (K) Survival curve of age of death in parents and offspring.
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