Recurrent Biallelic p.<scp>L347P <i>PINK1</i></scp> Variant in Polynesians with Parkinsonism and Isolated Dopa‐Responsive Dystonia

Morales‐Briceño, Hugo; Ong, Tien Lee; Duma, Stephen R.; Murray, Natalia; Pepper, Elizabeth; Tchan, Michel; Fung, Victor S.C.

doi:10.1002/mdc3.13467

Cited by 4 publications

(4 citation statements)

References 7 publications

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“…Specifically, the p.L347P variant appears to be a common cause of AR early‐onset PD in Southeast Asia and the Pacific Islands (proposed to reflect ancient migratory patterns of Austronesian races), and displays marked clinical heterogeneity ranging from mild PD (or even dopa‐responsive dystonia without parkinsonism), to cases with extremely severe motor complications (Video 7). 177,180,198 …”

Section: Resultsmentioning

confidence: 99%

“…the p.L347P variant appears to be a common cause of AR earlyonset PD in Southeast Asia and the Pacific Islands (proposed to reflect ancient migratory patterns of Austronesian races), and displays marked clinical heterogeneity ranging from mild PD (or even dopa-responsive dystonia without parkinsonism), to cases with extremely severe motor complications (Video 7). 177,180,198 In recent years, several novel PD-causative or related genes have been identified, notably in Asian populations. Variants in the CHCHD2 gene were linked to a late-onset AD form of PD (PARK22) in a large Japanese cohort.…”

Section: Pd-causative Genetic Variants In Asian Populationsmentioning

confidence: 99%

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Genetic Movement Disorders Commonly Seen in Asians

Jagota

Lim

Pal

et al. 2023

Movement Disord Clin Pract

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The increasing availability of molecular genetic testing has changed the landscape of both genetic research and clinical practice. Not only is the pace of discovery of novel disease-causing genes accelerating but also the phenotypic spectra associated with previously known genes are expanding. These advancements lead to the awareness that some genetic movement disorders may cluster in certain ethnic populations and genetic pleiotropy may result in unique clinical presentations in specific ethnic groups. Thus, the characteristics, genetics and risk factors of movement disorders may differ between populations. Recognition of a particular clinical phenotype, combined with information about the ethnic origin of patients could lead to early and correct diagnosis and assist the development of future personalized medicine for patients with these disorders. Here, the Movement Disorders in Asia Task Force sought to review genetic movement disorders that are commonly seen in Asia, including Wilson's disease, spinocerebellar ataxias (SCA) types 12, 31, and 36, Gerstmann-Sträussler-Scheinker disease, PLA2G6-related parkinsonism, adult-onset neuronal intranuclear inclusion disease (NIID), and paroxysmal kinesigenic dyskinesia. We also review common disorders seen worldwide with specific mutations or presentations that occur frequently in Asians.

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Section: Resultsmentioning

confidence: 99%

Section: Pd-causative Genetic Variants In Asian Populationsmentioning

confidence: 99%

Genetic Movement Disorders Commonly Seen in Asians

Jagota

Lim

Pal

et al. 2023

Movement Disord Clin Pract

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“…In contrast, the impact of environmental factors, such as exercise [115][116][117][118] or dietary patterns (e.g., caffeine or alcohol intake [84]) on disease progression is much less well defined. That said, much remains to be understood with respect to genotypephenotype correlations, e.g., patients with the exact same point mutation in genes linked to monogenic PD [98,[119][120][121][122] can sometimes still exhibit very different clinical courses, suggesting the presence of modifiers (genetic, epigenetic, and/or environmental) [5]. Even here, however, emerging evidence suggests a possibly more significant modifying role for genetic over environmental factors [123].…”

Section: Besides Causation/development Of Disease Genetic Factors Can...mentioning

confidence: 99%

Parkinson’s Disease is Predominantly a Genetic Disease

Lim,

Klein

2024

JPD

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The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene in the Contursi kindred in 1997 indisputably confirmed a genetic cause in a subset of Parkinson’s disease (PD) patients. Currently, pathogenic variants in one of the seven established PD genes or the strongest known risk factor gene, GBA1, are identified in ∼15% of PD patients unselected for age at onset and family history. At first sight, the steep increase in PD prevalence exceeding that of other neurodegenerative diseases may argue against a predominant genetic etiology. Notably, the principal genetic contribution in PD is conferred by pathogenic variants in LRRK2 and GBA1 and, in both cases, characterized by an overall late age of onset and age-related penetrance. In addition, polygenic risk plays a considerable role in PD. However, it is likely that, in the majority of PD patients, a complex interplay of aging, genetic, environmental, and epigenetic factors leads to disease development.5% of PD patients unselected for age at onset and family history. At first sight, the steep increase in PD prevalence exceeding that of other neurodegenerative diseases may argue against a predominant genetic etiology. Notably, the principal genetic contribution in PD is conferred by pathogenic variants in LRRK2 and GBA1 and, in both cases, characterized by an overall late age of onset and age-related penetrance. In addition, polygenic risk plays a considerable role in PD. However, it is likely that, in the majority of PD patients, a complex interplay of aging, genetic, environmental, and epigenetic factors leads to disease development.

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“…Finally, a biallelic p.L347P PINK1 variant has been identified in 12 Polynesians as a cause of EOPD with mixed features of parkinsonism and/or L-Dopa-responsive dystonia [84,85].…”

Section: Pink1mentioning

confidence: 99%

The Landscape of Monogenic Parkinson’s Disease in Populations of Non-European Ancestry: A Narrative Review

Koros,

Bougea,

Simitsi

et al. 2023

Genes

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Introduction: There has been a bias in the existing literature on Parkinson’s disease (PD) genetics as most studies involved patients of European ancestry, mostly in Europe and North America. Our target was to review published research data on the genetic profile of PD patients of non-European or mixed ancestry. Methods: We reviewed articles published during the 2000–2023 period, focusing on the genetic status of PD patients of non-European origin (Indian, East and Central Asian, Latin American, sub-Saharan African and Pacific islands). Results: There were substantial differences regarding monogenic PD forms between patients of European and non-European ancestry. The G2019S Leucine Rich Repeat Kinase 2 (LRRK2) mutation was rather scarce in non-European populations. In contrast, East Asian patients carried different mutations like p.I2020T, which is common in Japan. Parkin (PRKN) variants had a global distribution, being common in early-onset PD in Indians, in East Asians, and in early-onset Mexicans. Furthermore, they were occasionally present in Black African PD patients. PTEN-induced kinase 1 (PINK1) and PD protein 7 (DJ-1) variants were described in Indian, East Asian and Pacific Islands populations. Glucocerebrosidase gene variants (GBA1), which represent an important predisposing factor for PD, were found in East and Southeast Asian and Indian populations. Different GBA1 variants have been reported in Black African populations and Latin Americans. Conclusions: Existing data reveal a pronounced heterogeneity in the genetic background of PD. A number of common variants in populations of European ancestry appeared to be absent or scarce in patients of diverse ethnic backgrounds. Large-scale studies that include genetic screening in African, Asian or Latin American populations are underway. The outcomes of such efforts will facilitate further clinical studies and will possibly contribute to the identification of either new pathogenic mutations in already described genes or novel PD-related genes.

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Recurrent Biallelic p.L347P PINK1 Variant in Polynesians with Parkinsonism and Isolated Dopa‐Responsive Dystonia

Cited by 4 publications

References 7 publications

Genetic Movement Disorders Commonly Seen in Asians

Genetic Movement Disorders Commonly Seen in Asians

Parkinson’s Disease is Predominantly a Genetic Disease

The Landscape of Monogenic Parkinson’s Disease in Populations of Non-European Ancestry: A Narrative Review

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