An updated review of Parkinson's disease genetics and clinicopathological correlations

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Parkinson's disease (PD) is a common neurodegenerative disorder and can be seen in people from all races and geographical locations.1 With a prevalence of 1%–2% in the population aged over 65 years, PD is the major cause of degenerative parkinsonism, a clinical motor syndrome characterized by bradykinesia, resting tremor, muscle rigidity, and postural instability.2 The neuropathology of PD is characterized by a specific pattern of neuronal loss with the presence of α‐synuclein‐containing Lewy bodies (LB) in the surviving neurons.5 Nonetheless, some cases do not follow this classical pathological description, as we will further elaborate throughout the text.
Most PD cases are sporadic and of unknown etiology.1 However, over the past two decades, the knowledge regarding the underlying basis of this disorder has been rebuilt, partly due to the advances of genetics. Our understanding of PD has changed since the identification of familial forms of PD, the identification of gene mutations responsible for these familial forms, and the mapping of risk variants for the disease. Nonetheless, all known genes involved in monogenic forms of PD and risk polymorphisms combined explain only part of all PD cases. A portion of “missing heritability” remains hidden that will hopefully become known through the future development of more informative genetic probing techniques.
Clinical genetics aims at identifying mutations that cause a specific disorder. Following this line of thought, locus symbols were introduced in the genetic language to designate a specific chromosomal region that had been connected to a familial disorder with a yet unknown gene. With time, a number of inconsistencies with this classification scheme have arisen, warranting solutions. When observing the specific case of locus denomination on PD, one is able to confirm that both disease‐causing gene and risk factors have a locus symbol assignment, that there are still some missing locus symbols or some missing gene locus, and that there are cases of unconfirmed linkage or gene identification, and even erroneous linkages with the disease. So, in this article, we will summarize the current knowledge on PD genetics, discussing also the clinical and pathological features of each type, while applying a new classification based on the solution proposed by Marras et al.
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