The Ala53Thr mutation in the α‐synuclein gene in a Korean family with Parkinson disease

Cs, Ki; Ef, Stavrou; Davanos, Nikolaos; Lee, WY; Ej, Chung; Jy, Kim; Athanassiadou, Aglaia

doi:10.1111/j.1399-0004.2007.00781.x

Cited by 62 publications

(40 citation statements)

References 12 publications

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“…This mutation is prevalent mainly in Greece, suggesting a Founder Effect [Athanassiadou et al, 1999;Papadimitriou et al, 1999]. Since then, the same mutation has been detected in a Korean PD family [Ki et al, 2007], while recently, a Swedish family carrying a de novo p.Ala53Thr mutation was also identified [Puschmann et al, 2009]. In addition, the identification of two different SNCA mutations, namely, mutations p.Ala30Pro and p.Glu46Lys [Kruger et al, 1998;Zarranz et al, 2004], provides a sound genetic basis for the implication of SNCA point mutations in PD.…”

Section: Introductionmentioning

confidence: 67%

Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease

et al. 2010

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Genetic alterations in the alpha-synuclein (SNCA) gene have been implicated in Parkinson Disease (PD), including point mutations, gene multiplications, and sequence variations within the promoter. Such alterations may be involved in pathology through structural changes or overexpression of the protein leading to protein aggregation, as well as through impaired gene expression. It is, therefore, of importance to specify the parameters that regulate SNCA expression in its normal and mutated state. We studied the expression of SNCA alleles in a lymphoblastoid cell line and in the blood cells of a patient heterozygous for p.Ala53Thr, the first mutation to be implicated in PD pathogenesis. Here, we provide evidence that: (1) SNCA shows monoallelic expression in this patient, (2) epigenetic silencing of the mutated allele involves histone modifications but not DNA methylation, and (3) steady-state mRNA levels deriving from the normal SNCA allele in this patient exceed those of the two normal SNCA alleles combined, in matching, control individuals. An imbalanced SNCA expression in this patient is thus documented, with silencing of the p.Ala53Thr allele and upregulation of the wild-type-allele. This phenomenon is demonstrated for a first time in the SNCA gene, and may have important implications for PD pathogenesis.

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Section: Introductionmentioning

confidence: 67%

Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease

et al. 2010

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“…These variants of single nucleotide substitution in PINK1 were not found in 100 normal controls. One patient had heterozygous c.203G>A [p.A53T] mutation in SNCA who turned out to be a family member of a previously reported case [12]. Mutations of the above genes are summarized in Table 2.…”

Section: Resultsmentioning

confidence: 99%

Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease

Choi

Woo

et al. 2008

Neurogenetics

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Mutations in five PARK genes (SNCA, PARKIN, DJ-1, PINK1, and LRRK2) are well-established genetic causes of Parkinson disease (PD). Recently, G2385R substitution in LRRK2 has been determined as a susceptibility allele in Asian PD. The objective of this study is to determine the frequency of mutations in these PARK genes in a Korean early-onset Parkinson disease (EOPD) cohort. The authors sequenced 35 exons in SNCA, PARKIN, DJ-1, PINK1, and LRRK2 in 72 unrelated EOPD (age-at-onset ≤50) recruited from ten movement disorders clinics in South Korea. Gene dosage change of Neurogenetics

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“…Out of the three missense mutations, the first identified, p.A53T, seems to be by far the most frequent one and was found in one Italian, eight Greek, two Korean, and one Swedish family (Polymeropoulos et al 1997;Athanassiadou et al 1999;Spira et al 2001;Ki et al 2007;Choi et al 2008;Puschmann et al 2009). The p.A30P and p.E46K mutations were identified in one family each (Kruger et al 1998;Zarranz et al 2004).…”

Section: Monogenic Forms Of Pdmentioning

confidence: 99%

Genetics of Parkinson's Disease

Klein

Westenberger

2012

Cold Spring Harbor Perspectives in Medicine

1,115

780

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Fifteen years of genetic research in Parkinson's disease (PD) have led to the identification of several monogenic forms of the disorder and of numerous genetic risk factors increasing the risk to develop PD. Monogenic forms, caused by a single mutation in a dominantly or recessively inherited gene, are well-established, albeit relatively rare types of PD. They collectively account for about 30% of the familial and 3%-5% of the sporadic cases. In this article, we will summarize the current knowledge and understanding of the molecular genetics of PD. In brief, we will review familial forms of PD, basic genetic principles of inheritance (and their exceptions in PD), followed by current methods for the identification of PD genes and risk factors, and implications for genetic testing.

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The Ala53Thr mutation in the α‐synuclein gene in a Korean family with Parkinson disease

Cited by 62 publications

References 12 publications

Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease

Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease

Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease

Genetics of Parkinson's Disease

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