ND00139

Overview

Repository

NINDS Repository

Subcollection

Parkinsonism

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Subject Type

family with at least 3 members, including 1 proband, not a trio

Family Type

MULTIGENERATIONAL FAMILIES - MORE THAN ONE AFFECTED

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Species

Homo sapiens

Common Name

Human

Characterizations

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.

Gene

LRRK2

Chromosomal Location

12q12

Allelic Variant 1

; WILDTYPE

Identified Mutation

WILDTYPE for GLY2019

Gene

LRRK2

Chromosomal Location

12q12

Allelic Variant 2

; WILDTYPE

Identified Mutation

WILDTYPE for GLY2019

Publications

Pitcairn C, Murata N, Zalon AJ, Stojkovska I, Mazzulli JR, Impaired Autophagic-Lysosomal Fusion in Parkinson's Patient Midbrain Neurons Occurs through Loss of ykt6 and Is Rescued by Farnesyltransferase Inhibition The Journal of neuroscience : the official journal of the Society for Neuroscience43:2615-2629 2022

PubMed ID: 36788031

Zafar F, Valappil RA, Kim S, Johansen KK, Chang ALS, Tetrud JW, Eis PS, Hatchwell E, Langston JW, Dickson DW, Schüle B, Genetic fine-mapping of the Iowan NPJ Parkinson's disease4:18 2017

PubMed ID: 29928688

Ross OA, Braithwaite AT, Skipper LM, Kachergus J, Hulihan MM, Middleton FA, Nishioka K, Fuchs J, Gasser T, Maraganore DM, Adler CH, Larvor L, Chartier-Harlin MC, Nilsson C, Langston JW, Gwinn K, Hattori N, Farrer MJ, Genomic investigation of alpha-synuclein multiplication and parkinsonism Annals of neurology63:743-50 2008

PubMed ID: 18571778

Fuchs J, Nilsson C, Kachergus J, Munz M, Larsson EM, Schüle B, Langston JW, Middleton FA, Ross OA, Hulihan M, Gasser T, Farrer MJ, Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication Neurology68:916-22 2007

PubMed ID: 17251522

Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K, alpha-Synuclein locus triplication causes Parkinson's disease. Science302(5646):841 2003

PubMed ID: 14593171

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

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

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

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

Waters CH, Miller CA, Autosomal dominant Lewy body parkinsonism in a four-generation family. Ann Neurol35(1):59-64 1994

PubMed ID: 8285594