Journal
PARKINSONISM & RELATED DISORDERS
Volume 78, Issue -, Pages 105-108Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2020.07.023
Keywords
Parkinson's disease; PINK1; Pathology; Lewy bodies; Deep brain stimulation
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Funding
- St. Olav's Hospital
- Reberg's Legacy
- Canada Excellence Research Chairs Program
- Leading Edge Endowment Funds by the Province of British Columbia
- Genome BC support through the Dr. Donald Rix BC Leadership Chair
- Peter Cundill Foundation
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Introduction: Biallelic mutations in PTEN-induced putative kinase 1 (PINK1) is a relatively common cause of autosomal recessive early-onset Parkinson's disease (PD). However, only three PINK1 patients with brain autopsy have been reported in the literature. Methods: We describe the clinical and pathological characteristics of a patient with early-onset PD. We screened for copy number variants SNCA, PRKN, PINK1, DJ-1, ATP13A2, LPA and TNFRSF9 by multiplex ligationdependent probe amplification (MLPA), and subsequently we performed whole-exome sequencing. Results: Clinically the patient presented with typical parkinsonism that responded well to levodopa. After 23 years of disease she had a bilateral GPi deep brain stimulation (DBS) surgery. Genetic analyses revealed a heterozygous exon 4-5 deletion and a homozygous exon 1 [c. 230T > C (p.Leu77Pro)] mutation in PINK1. Post mortem neuropathological examination after more than 30 years of disease revealed gliosis and a large loss of melanin-containing neurons in the substantia nigra. Lewy body pathology was evident in substantia nigra, temporal cortex, locus coeruleus and the parahippocampal region. Conclusion: We describe the first clinical and pathological characterization of a PINK1 patient with a typical disease presentation and long disease duration. Previous reports describe two patients with Lewy-related pathologies, albeit with differential distribution, and one patient with no Lewy-related pathology. Hence, it seems that only two patients with parkinsonism due to mutations in PINK1 are consistent with alpha-synucleinopathy distribution like that seen in the majority of cases with sporadic PD. Our data further extend the clinicopathological characterization of PINK1-associated PD.
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