Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia

Archives of Neurology
Takeshi IkeuchiAtsushi Ishikawa

Abstract

Multiplication of the alpha-synuclein gene (SNCA) (OMIM 163890) has been identified as a causative mutation in hereditary Parkinson disease or dementia with Lewy bodies. To determine the genetic, biochemical, and neuropathologic characteristics of patients with autopsy-confirmed autosomal dominant Lewy body disease, with particular reference to the dosage effects of SNCA. Four-generation family study. Academic research. Patients We fractionated samples extracted from frozen brain tissues of 4 patients for biochemical characterization, followed by immunoblot analysis. We determined the dosages of SNCA and its surrounding genes by quantitative polymerase chain reaction analysis. Quantitative polymerase chain reaction analysis revealed that 3 patients were heterozygous for SNCA duplication and 1 patient was homozygous for SNCA duplication. The homozygous patient showed earlier age at onset and earlier death, with more severe cognitive impairment than the heterozygous patients. Biochemical analysis revealed that phosphorylated alpha-synuclein accumulated in the sarkosyl-insoluble urea-extracted fraction of the brains of the patients. Pathologically confirmed Lewy body disease clinically characterized by progressive parkinsonism and...Continue Reading

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