GM15845

GM15845 LCL from B-Lymphocyte

Description:

PARKINSON DISEASE,FAMILIAL, TYPE 1; PARK1
SYNUCLEIN, ALPHA; SNCA

Affected:

No Data

Sex:

Female

Age:

59 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of the Nervous System

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Family Member

Relation to Proband

aunt

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

At risk; normal examination with no complaints; three siblings died of Parkinson disease with onset at 25-45 years; one daughter with essential tremor; affected nephew is GM15009 and affected nieces 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 (ND27756) with additional family members

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

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.

Phenotypic Data

Remarks

Publications

Stojkovska I, Wani WY, Zunke F, Belur NR, Pavlenko EA, Mwenda N, Sharma K, Francelle L, Mazzulli JR, Rescue of a-synuclein aggregation in Parkinson's patient neurons by synergistic enhancement of ER proteostasis and protein trafficking Neuron110:436-451.e11 2021

PubMed ID: 34793693

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

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

PubMed ID: 8285594