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Genotype-Phenotype Correlations in Parkinson Disease

Puschmann, Andreas LU and Wszolek, Zbigniew K (2014) In Movement Disorders: Genetics and Models, 2nd Edition p.259-285
Abstract
Mutations in four autosomal dominant (SNCA, LRRK2, VPS35, EIF4G1) and three recessive genes (PARK2, PINK1, PARK7/DJ1) are known to cause Parkinson disease (PD). This chapter describes the clinical and pathological phenotypes associated with mutations in these genes. We systematically reviewed the phenotypes associated with all known pathogenic mutations in the dominant genes. SNCA point mutations and genomic multiplications cause a disorder with akinetic-rigid Parkinsonism, dysautonomia, cognitive decline, myoclonus, and pronounced alpha-synuclein pathology. LRRK2 mutations cause tremor-dominant or akinetic-rigid Parkinsonism with variable pathology. Our knowledge about the newly described genes VPS35 and EIF4G1 is still limited.... (More)
Mutations in four autosomal dominant (SNCA, LRRK2, VPS35, EIF4G1) and three recessive genes (PARK2, PINK1, PARK7/DJ1) are known to cause Parkinson disease (PD). This chapter describes the clinical and pathological phenotypes associated with mutations in these genes. We systematically reviewed the phenotypes associated with all known pathogenic mutations in the dominant genes. SNCA point mutations and genomic multiplications cause a disorder with akinetic-rigid Parkinsonism, dysautonomia, cognitive decline, myoclonus, and pronounced alpha-synuclein pathology. LRRK2 mutations cause tremor-dominant or akinetic-rigid Parkinsonism with variable pathology. Our knowledge about the newly described genes VPS35 and EIF4G1 is still limited. Homozygous or compound heterozygous mutations in the recessive PD genes cause Parkinsonism with an early or very-early onset, but many different mutations are found in these genes and genotype-phenotype correlations are based on low numbers of patients per mutation. Homozygous mutations in GBA may cause Parkinsonism, usually in patients who have Gaucher disease, whereas heterozygous GBA mutations are genetic risk factors for PD. The monogenic forms of PD represent distinct subtypes of this heterogeneous disorder. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Parkinsons disease Genetics
categories
Higher Education
in
Movement Disorders: Genetics and Models, 2nd Edition
editor
LeDoux, Mark S
pages
259 - 285
publisher
Elsevier
external identifiers
  • Scopus:84943231398
ISBN
9780124051959
9780124055162
language
English
LU publication?
yes
id
183e1af1-a1fa-48b3-a08b-5eec30a14a1e (old id 3990768)
date added to LUP
2015-06-22 08:59:32
date last changed
2016-10-13 04:42:34
@misc{183e1af1-a1fa-48b3-a08b-5eec30a14a1e,
  abstract     = {Mutations in four autosomal dominant (SNCA, LRRK2, VPS35, EIF4G1) and three recessive genes (PARK2, PINK1, PARK7/DJ1) are known to cause Parkinson disease (PD). This chapter describes the clinical and pathological phenotypes associated with mutations in these genes. We systematically reviewed the phenotypes associated with all known pathogenic mutations in the dominant genes. SNCA point mutations and genomic multiplications cause a disorder with akinetic-rigid Parkinsonism, dysautonomia, cognitive decline, myoclonus, and pronounced alpha-synuclein pathology. LRRK2 mutations cause tremor-dominant or akinetic-rigid Parkinsonism with variable pathology. Our knowledge about the newly described genes VPS35 and EIF4G1 is still limited. Homozygous or compound heterozygous mutations in the recessive PD genes cause Parkinsonism with an early or very-early onset, but many different mutations are found in these genes and genotype-phenotype correlations are based on low numbers of patients per mutation. Homozygous mutations in GBA may cause Parkinsonism, usually in patients who have Gaucher disease, whereas heterozygous GBA mutations are genetic risk factors for PD. The monogenic forms of PD represent distinct subtypes of this heterogeneous disorder.},
  author       = {Puschmann, Andreas and Wszolek, Zbigniew K},
  editor       = {LeDoux, Mark S},
  isbn         = {9780124051959},
  keyword      = {Parkinsons disease Genetics},
  language     = {eng},
  pages        = {259--285},
  publisher    = {ARRAY(0x866e798)},
  series       = {Movement Disorders: Genetics and Models, 2nd Edition},
  title        = {Genotype-Phenotype Correlations in Parkinson Disease},
  year         = {2014},
}