Juvenile <scp>PLA2G6</scp>‐Parkinsonism Due to Indian ‘Asian’ p.<scp>R741Q</scp> Mutation, and Response to <scp>STN DBS</scp>

Ravat, Parthvi; Shinde, Swati; Shinde, Shilpa R; Bangar, Santosh; Nayak, Naren; Agarwal, Poojan

doi:10.1002/mds.28950

Cited by 4 publications

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“…2 It also adds to the hitherto scant evidence that deep brain stimulation (DBS) may be effective for managing symptoms and early complications of dopaminergic treatment in this disorder. 1,2 Further cases of PLA2G6-parkinsonism are in keeping with the main findings of our work and confirm the core phenotype depicted therein, 2-7 including another patient we identified (Table 1, Case S1). This is a 35-year-old female born to consanguineous Pakistani parents after uncomplicated pregnancy and birth.…”

supporting

confidence: 90%

“…2 Regardless of the extent of levodopa responsiveness, most cases recently reported developed early dyskinesia, 3,6,7 which are often prominent in the lower face, as also demonstrated by Ravat et al's video. 1 In this context, we point out that peak-dose dystonic dyskinesia and spasms affecting the oromandibular region in response to low-dose levodopa are not uncommon in PLA2G6-parkinsonism, with spasms resembling those seen in multiple system atrophy (Video S1, Case S2). 8 Our deep phenotyping approach revealed several diagnostic clues to PLA2G6-parkinsonism, for which some mutant alleles show geographical clustering and disease-modifying treatments are under investigation.…”

mentioning

confidence: 85%

“…In their discussion, Sambin et al properly addressed the contribution of increased dopamine turnover in delaying the clinical onset of PD emphasizing the role of increased dopamine synthesis, as measured with [ 18 F]-L-DOPA. 1 In addition, it should be mentioned that a functional relation has been demonstrated between increased dopamine turnover and lower DAT transporter. 5 It is therefore not surprising that presynaptic compensatory changes include a reduction in the membrane DAT binding, which is also evident in early-disease stages and serves to optimize dopamine utilization by surviving nerve terminals.…”

Section: Data Availability Statementmentioning

confidence: 99%

“…

We are grateful for Ravat et al's interest in our article on PLA2G6-parkinsonism. 1,2,3 They reported an additional case showing some clinicoradiological diagnostic hints we highlighted, including young onset of levodopa-responsive parkinsonism, occurrence of truncal dystonia and cerebellar signs, early development of levodopa-induced dyskinesia, and presence of cerebellar atrophy as well as possible lack of iron deposition on brain MRI. 2 Their case 1 reinforces our observation that NM_003560.4(PLA2G6):c.2222G > A (p. Arg741Gln) is the most frequent variant in Indian cases of PLA2G6-parkinsonism.

…”

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confidence: 92%

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Reply to: Juvenile PLA2G6‐parkinsonism due to Indian ‘Asian’ p.R741Q mutation, and response to STN DBS

et al. 2022

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We are grateful for Ravat et al.'s interest in our article on PLA2G6-parkinsonism. 1,2,3 They reported an additional case showing some clinicoradiological diagnostic hints we highlighted, including young onset of levodopa-responsive parkinsonism, occurrence of truncal dystonia and cerebellar signs, early development of levodopa-induced dyskinesia, and presence of cerebellar atrophy as well as possible lack of iron deposition on brain MRI. 2 Their case 1 reinforces our observation that NM_003560.4(PLA2G6):c.2222G > A (p. Arg741Gln) is the most frequent variant in Indian cases of PLA2G6-parkinsonism. 2 It also adds to the hitherto scant evidence that deep brain stimulation (DBS) may be effective for managing symptoms and early complications of dopaminergic treatment in this disorder. 1,2 Further cases of PLA2G6-parkinsonism are in keeping with the main findings of our work and confirm the core phenotype depicted therein, 2-7 including another patient we identified (Table 1, Case S1). This is a 35-year-old female born to consanguineous Pakistani parents after uncomplicated pregnancy and birth. She experienced occasional falls during childhood and required crutches because of lower-limb spasticity since her teenage years. Despite a mild learning difficulty, she completed her secondary education at a normal school. At age 16, she had a psychotic FIG. 1. Sagittal T1 (A) and axial T2 (B) magnetic resonance (MR) images show mild cerebellar atrophy. 99mTc-TRODAT SPECT scan (C) reveals bilateral, asymmetric reduction of tracer uptake, more prominent on the left side, with putaminal uptake more reduced than the caudate bilaterally, consistent with the pattern seen in Parkinson's disease. [Color figure can be viewed at wileyonlinelibrary.com]

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supporting

confidence: 90%

mentioning

confidence: 85%

Section: Data Availability Statementmentioning

confidence: 99%

“…

…”

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confidence: 92%

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Reply to: Juvenile PLA2G6‐parkinsonism due to Indian ‘Asian’ p.R741Q mutation, and response to STN DBS

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“…In a Chinese study, variants in PLA2G6 were not particularly rare and accounted for 1.89% of early-onset PD [23]. An Indian group described juvenile PLA2G6-Parkinsonism due to a p.R741Q mutation [109]. A Chinese population study showed that the Pro2Leu variant in CHCHD2 may be related to the development of PD among Asians [110].…”

Section: Other Rare Genesmentioning

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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Motor and non-motor responses of STN DBS in early onset PLA2G6 related Parkinsonism with compound heterozygous mutation from China

Chen¹,

Zhang²,

Zhang

et al. 2023

Parkinsonism & Related Disorders

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Juvenile PLA2G6‐Parkinsonism Due to Indian ‘Asian’ p.R741Q Mutation, and Response to STN DBS

Cited by 4 publications

References 5 publications

Reply to: Juvenile PLA2G6‐parkinsonism due to Indian ‘Asian’ p.R741Q mutation, and response to STN DBS

Reply to: Juvenile PLA2G6‐parkinsonism due to Indian ‘Asian’ p.R741Q mutation, and response to STN DBS

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

Motor and non-motor responses of STN DBS in early onset PLA2G6 related Parkinsonism with compound heterozygous mutation from China

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