Description:
PARKINSON DISEASE,FAMILIAL, TYPE 1; PARK1
SYNUCLEIN, ALPHA; SNCA
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of the Nervous System |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Family Member
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2
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Relation to Proband
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maternal first cousin
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Gene |
SNCA |
| Chromosomal Location |
4q21 |
| Allelic Variant 1 |
163890.0003; PARKINSON DISEASE, TYPE 1; PARK1 |
| Identified Mutation |
TRIPLICATION; By quantitative PCR amplification of SNCA exons in an individual with parkinsonism from a family reported by Waters and Miller [Ann. Neurol. 35: 59-64 (1994)], Singleton et al. [Science 302: 841 (2003)] found evidence consistent with whole gene triplication. The triplicated region contains an estimated 17 genes, including SNCA. Carriers of the triplication are predicted to have 4 fully functional copies of SNCA, with doubling of the effective load of the estimated 17 genes. The authors suggested that increased dosage of SNCA is the cause of PD in this family, and noted that the disease process may resemble the etiology of Alzheimer disease in Down syndrome (190685) with overexpression of the APP gene due to chromosome 21 trisomy. |
| Remarks |
Onset at age 24; severe bradykinesia; dopamine responsive; resting tremor; rigidity; unable to speak; fed through PEG tube; slow walk; needs assistance to stand; mother and maternal uncle and aunt were affected; affected cousins are GM15010 and GM15844; molecular characterization of this family found evidence consistent with whole gene triplication with the triplicated region containing an estimated 17 genes, including SNCA; carriers of the triplication are predicted to have 4 fully functional copies of SNCA, the increased dosage of SNCA suggested as the cause of PD in this family; this sample was formerly classified as PARK4 [605543]; this sample is also included in the NINDS Repository (ND00196) with additional family members |
| Caviness JN, Gwinn-Hardy K, Adler CH, Muenter MD, Electrophysiological observations in hereditary parkinsonism-dementia with Lewy body pathology. Mov Disord15(1):140-5 2000 |
| PubMed ID: 10634254 |
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| Gwinn-Hardy K, Mehta ND, Farrer M, Maraganore D, Muenter M, Yen SH, Hardy J, Dickson DW, Distinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p. Acta Neuropathol (Berl)99(6):663-72 2000 |
| PubMed ID: 10867800 |
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| Farrer M, Gwinn-Hardy K, Muenter M, DeVrieze FW, Crook R, Perez-Tur J, Lincoln S, Maraganore D, Adler C, Newman S, MacElwee K, McCarthy P, Miller C, Waters C, Hardy J, A chromosome 4p haplotype segregating with Parkinson's disease and postural tremor. Hum Mol Genet8(1):81-5 1999 |
| PubMed ID: 9887334 |
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| Gwinn-Hardy K, Evidente VG, Waters C, Muenter MD, Hardy J, L-dopa slows the progression of familial parkinsonism. Lancet353(9167):1850-1 1999 |
| PubMed ID: 10359414 |
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| Muenter MD, Forno LS, Hornykiewicz O, Kish SJ, Maraganore DM, Caselli RJ, Okazaki H, Howard FM Jr, Snow BJ, Calne DB, Hereditary form of parkinsonism--dementia. Ann Neurol43(6):768-81 1998 |
| PubMed ID: 9629847 |
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| Waters CH, Miller CA, Autosomal dominant Lewy body parkinsonism in a four-generation family. Ann Neurol35(1):59-64 1994 |
| PubMed ID: 8285594 |
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