Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. Five to ten percent of patients have monogenic form of the disease, while most of sporadic PD cases are caused by the combination of genetic and environmental factors. Microtubule-associated protein tau (MAPT) has been appointed as one of the most important risk factors for several neurodegenerative diseases including PD. MAPT is characterized by an inversion in chromosome 17 resulting in two distinct haplotypes H1 and H2. Studies described a significant association of MAPT H1j subhaplotype with PD risk, while H2 haplotype was associated with Parkinsonism, particularly to its bradykinetic component. We report here an isolated case displaying an akinetic-rigid form of PD, with age of onset of 41 years and a good response to levodopa, who developed dementia gradually during the seven years of disease progression. The patient does not carry the LRRK2 G2019S mutation, copy number variations, nor pathogenic and rare variants in known genes associated with PD. MAPT subhaplotype genotyping revealed that the patient has the H1j/H2 diplotype, his mother H1j/H1j, his two healthy brothers H1j/H1v and his deceased father was by deduction H1v/H2. The H1j/H2 diplotype was shown in a total of 3 PD patients among 80, who also did not have known PD-causing mutation and in 1 out of 92 healthy individual controls. The three patients with this diplotype all have a similar clinical phenotype. Our results suggest that haplotypes H1j and H2 are strong risk factor alleles, and their combination could be responsible for early onset of PD with dementia.
Highlights
Parkinson’s disease (PD) is a neurodegenerative condition that results in progressive movement disorder associated with nonmotor symptoms [1]
Gene-panel next-generation sequencing (NGS) with 25 genes associated with PD and overlapping phenotypes (Supplementary Materials) was performed in the patient and his mother using the Ion Proton System for Next-Generation Sequencing. e library was prepared by the Ion Chef System according to the Ion AmpliSeq Kit for Chef DL8 instructions
We received in the Department of Neurology of Rabat a patient who was diagnosed with an akinetic-rigid form of PD and an early age of onset of 43 years old. e follow-up of the patient over a period of 7 years showed, in addition to motor fluctuations, a mild cognitive decline
Summary
Parkinson’s disease (PD) is a neurodegenerative condition that results in progressive movement disorder associated with nonmotor symptoms [1]. We report a 48-year-old Moroccan patient displaying PD with dementia who had no known PDcausing mutation, but who carried a specific diplotype H1j/ H2 of MAPT, suggesting that these two haplotypes are risk factor alleles, and their combination could be responsible for early onset PD with dementia.
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