The heterozygous A53T mutation in the alpha-synuclein gene in a Chinese Han patient with Parkinson disease: case report and literature review

J Neurol. 2016 Oct;263(10):1984-92. doi: 10.1007/s00415-016-8213-1. Epub 2016 Jul 8.

Abstract

The missense mutation A53T of alpha-synuclein gene (SNCA) was reported to be a rare but definite cause of sporadic and familial Parkinson disease (PD). It seemed to be restricted geographically in Greece and Italy. We aimed to identify the SNCA mutations in a Chinese PD cohort. Ninety-one early onset PD patients or familial PD probands were collected consecutively for the screening of PD-related genes. The genetic analysis was carried out by target sequencing of the exons and the corresponding flanking regions of the PD-related genes using Illumina HiSeq 2000 sequencer and further confirmed by Sanger sequencing or restriction fragment length polymorphism. Dosage mutations of exons in these genes were carried out by multiple ligation-dependent probe amplification. Among the 91 patients, we found only one heterozygous mutation of SNCA A53T, in a 23-year-old male patient with negative family history. The [(11)C]-2β-carbomethoxy-3β-(4-fluorophenyl) tropan (CFT) PET and PD-related spatial covariance pattern (PDRP) via [(18)F]-fluorodeoxyglucos (FDG) PET confirmed a typical pattern of PD. After examining his parents, we found his mother was an asymptomatic carrier, with declined hand dexterity detected by quantitative motor tests. Reduced dopamine transporter uptake of his mother was identified by CFT PET, and abnormal PDRP pattern was found by FDG PET. Our investigation expanded the clinical and genetic spectrum of Chinese PD patients, and we suggested SNCA mutations to be screened in familial and early onset Chinese PD patients.

Keywords: A53T alpha-synuclein mutation; Dopamine transporter; PET; Parkinson disease; Parkinson’s disease-related spatial covariance pattern.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • China / epidemiology
  • China / ethnology
  • DNA Mutational Analysis
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / ethnology
  • Parkinson Disease / genetics*
  • Positron-Emission Tomography
  • Young Adult
  • alpha-Synuclein / genetics*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • alpha-Synuclein