Title:Parkinson Disease Genetics: A "Continuum" from Mendelian to Multifactorial Inheritance
Volume: 14
Issue: 8
Author(s): S. Petrucci, F. Consoli and E.M. Valente
Affiliation:
Keywords:
Genetics, monogenic, multifactorial, Parkinson disease, parkinsonism, risk factor.
Abstract: Parkinson Disease (PD) is a common neurodegenerative disorder of intricate etiology, caused by
progressive loss of aminergic neurons and accumulation of Lewy bodies. The predominant role of genetics in
the etiology of the disease has emerged since the identification of the first pathogenetic mutation in SNCA
(alpha-synuclein) gene, back in 1997. Mendelian parkinsonisms, a minority among all PD forms, have been
deeply investigated, with 19 loci identified. More recently, genome wide association studies have provided
convincing evidence that variants in some of these genes, as well as in other genes, may confer an increased
risk for late onset, sporadic PD. Moreover, the finding that heterozygous mutations in the GBA gene (mutated
in Gaucher disease) are among the strongest genetic susceptibility factors for PD, has widened the scenario of
PD genetic background to enclose a number of genes previously associated to distinct disorders, such as
genes causative of spinocerebellar ataxias, mitochondrial disorders and fragile X syndrome. At present, the
genetic basis of PD defines a continuum from purely mendelian forms (such as those caused by autosomal
recessive genes) to multifactorial inheritance, resulting from the variable interplay of many distinct genetic
variants and environmental factors.