Multiple Pathways including Environmental Factors that Lead to a Specific Phenotype with Later Onset

Moyra Smith

in Phenotypic Variation

Published on behalf of Oxford University Press

Published in print February 2011 | ISBN: 9780195379631
Published online October 2012 | e-ISBN: 9780199975211 | DOI:
Multiple Pathways including Environmental Factors that Lead to a Specific Phenotype with Later Onset

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  • Clinical Genetics
  • Clinical Cytogenetics and Molecular Genetics


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This chapters looks first at Parkinson's Disease, the characteristic feature of which is degeneration of dopaminergic neurons in the substantia nigra. Degeneration of other neurons, particularly in the brain stem, may occur. The phenotypic features of Parkinson’s disease include slowed movements, tremor, and rigidity after loss of 50 to 70 % of the dopaminergic neurons. In some patients there may be autonomic dysfunction and cognitive impairment. Insight into pathogenesis of sporadic Parkinson’s disease was achieved through findings of specific gene defects that lead to monogenic forms of Parkinson’s disease. The synuclein gene (SNCA) on chromosome 4q21 was identified and characterized following linkage studies in Parkinson’s disease. Copy number changes or mutations in this gene may lead to Parkinson’s disease. Alpha synuclein is a key component of Lewy bodies and Lewy neurites, which are characteristic features of Parkinson’s disease. A key factor in generation of Parkinson’s disease is overexpression of alpha synuclein. LRRK2 is a large gene of 144 kb with 31 exons. It encodes a 2,527-amino-acid protein. Parkinson’s disease results from missense mutations in this gene. Kufor Rakeb syndrome is an early-onset Parkinson’s disease that is associated with pyramidal degeneration and dementia. It is inherited as an autosomal recessive disease. The chapter then looks at complement factors: gene- environment interations and phenotyipc effects. Complement in the alternate pathway plays a role in the removal of immune complexes and of damaged cells. Complement factor H (CFH) is a key factor for regulation of the alternate complement pathway. In fluid phase and on cell surfaces it restricts excessive activation of that pathway. The chapter discusses CFH mutations in membrano-proliferative glomerulonephritis and atypical hemolytic uremic syndrome and genomic architecture in the CFH gene region.

Chapter.  2526 words. 

Subjects: Clinical Genetics ; Clinical Cytogenetics and Molecular Genetics

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