A Peruvian family with a novel PARK2 mutation: Clinical and pathological characteristics. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Cornejo-Olivas, Mario R.; Torres, Luis; Mata, Ignacio F.; Mazzetti, Pilar; Rivas, Diana; Cosentino, Carlos; Inca-Martinez, Miguel; Cuba, Juan M.; Zabetian, Cyrus P.; Leverenz, James B.
• Is Part Of: Parkinsonism & related disorders. Volume 21:Issue 5(2015)
• Page Start: 444
• Page End: 448
• Publication Date: 2015-05
• Subjects: Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2015.01.005
• Languages: English
• ISSNs: 1353-8020

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Background</title> <p id="abspara0010">Mutations in <italic>PARK2</italic> result in autosomal recessive young onset Parkinson's disease (YOPD). Although there have been a number of reports on the clinical characteristics of <italic>PARK2</italic>-related PD, there is limited information available on the associated neuropathologic changes.</p> </sec> <sec> <title id="sectitle0020">Design</title> <p id="abspara0015">We describe the clinical and pathological characteristics of a Peruvian family with YOPD. The proband and one unaffected sibling were screened for <italic>PARK2</italic> dosage and point mutations. One affected sibling had detailed neuropathologic examination.</p> </sec> <sec> <title id="sectitle0025">Setting</title> <p id="abspara0020"> <italic>Instituto Nacional de Ciencias Neurologicas</italic> (INCN) in Lima, Peru.</p> </sec> <sec> <title id="sectitle0030">Results</title> <p id="abspara0025">The proband and two of her four siblings developed YOPD and both parents were unaffected. The clinical course has been characterized by akinetic-rigid parkinsonism predominantly affecting the lower limbs and dyskinesias. Analysis of <italic>PARK2</italic> showed that the proband is compound heterozygous for a novel acceptor splice site mutation in intron 5 (IVS5-1G>A) and an exon 7 deletion. Neuropathologic assessment of an affected sibling revealed severe neuronal loss in the substantia nigra (SN) and loss of tyrosine hydroxylase immunopositive fibers in the striatum. No Lewy body pathology was observed using standard histology or immunohistochemistry for α-synuclein.</p> </sec> <sec> <title id="sectitle0035">Conclusions</title> <p id="abspara0030">Consistent with most neuropathologic reports of patients with <italic>PARK2</italic> mutations, we did not observe Lewy body inclusions, despite marked SN degeneration and severe dopaminergic denervation of the striatum. These data describe a novel splice site mutation and further extend the clinicopathological characterization of <italic>PARK2</italic>-associated PD.</p> </sec> </abstract>