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Adult-Onset PLA2G6-Associated Neurodegeneration (PLAN): A Clinical, Imaging and Genetic Profile Review
Published online by Cambridge University Press: 07 July 2025
Abstract
Background:
Adult-onset PLA2G6-associated neurodegeneration (PLAN) has a diverse phenotypic presentation.
Objective:
Detailed description of the clinical, imaging and genetic profile of adult-onset PLAN; comparison of the Indian cohort with Asian, Middle East and European cohorts; genotype–phenotype correlations; and determination of ethnic phenotypic and genotypic differences of adult-onset PLAN.
Methods:
Report of two patients of adult-onset PLAN and review of reported cases of adult-onset PLAN since 2015 from Indian, Asian, Middle East and European cohorts.
Results:
There were 12 cases in the Indian cohort, 45 in the Asian cohort, 10 in the Middle East cohort and 17 in European cohort. Patients in the Indian and Asian cohorts had a later age at onset as compared to the Middle East and European cohorts. The median duration of disease was similar among all cohorts. Dystonia, myoclonus and gaze palsy were common in the Indian cohort; parkinsonism and tremor in the Asian cohort; parkinsonism, tremor, spasticity and cognitive impairment in the Middle East cohort; and parkinsonism and behavioural disturbances in the European cohort. Early-onset parkinsonism was common in all cohorts. Mineralisation on MRI was less frequent in the Asian and Middle East cohorts. Cerebral/cerebellar atrophy was less frequent in the Asian cohort. The homozygous missense variant (c.2222G > A,p.R741Q) was common in the Indian and Middle East cohorts, whereas the homozygous/compound heterozygous variant (c.991G > T, p.D331Y) was the most common variant in the Asian cohort. Milder clinical and neuroimaging phenotypes were noted with c.991G > T (p.D331Y) variant and a relatively severe phenotype in c.2222G > A,p.R741Q variant.
Conclusion:
Adult-onset PLAN has a variable phenotype. We found ethnic phenotypic and imaging differences among the cohorts.
Résumé
La neurodégénérescence associée au gène PLA2G6 (PLAN), tardive : revue des caractéristiques cliniques, d’imagerie et génétiques.
La neurodégénérescence associée au gène PLA2G6 (PLAN), tardive, qui se manifeste à l’âge adulte, présente divers tableaux phénotypiques.
L’étude visait à dresser un tableau détaillé des caractéristiques cliniques, d’imagerie et génétiques de la PLAN tardive; à établir des comparaisons entre la cohorte indienne et la cohorte multiethnique : asiatique, moyenne-orientale et européenne, ainsi que des corrélations entre génotype et phénotype; et à relever des différences phénotypiques et génotypiques de la maladie entre les groupes ethniques.
L’étude repose sur deux rapports de patients atteints de la maladie PLAN tardive et sur l’examen de cas déclarés de cette maladie depuis 2015, dans les cohortes indienne, asiatique, moyenne-orientale et européenne.
Les cas étaient répartis ainsi : 12, dans la cohorte indienne; 45, dans la cohorte asiatique; 10, dans la cohorte moyenne-orientale et 17, dans la cohorte européenne. Les patients dans les cohortes indienne et asiatique étaient plus âgés que ceux dans les cohortes moyenne-orientale et européenne aux premières manifestations de la maladie. La durée médiane de la PLAN était comparable dans toutes les cohortes. La dystonie, la myoclonie et la paralysie du regard étaient fréquentes dans la cohorte indienne; le parkinsonisme et les tremblements, dans la cohorte asiatique; le parkinsonisme, les tremblements, la spasticité et les troubles cognitifs, dans la cohorte moyenne-orientale; enfin, le parkinsonisme et les troubles du comportement, dans la cohorte européenne. Le parkinsonisme précoce (EOP) était fréquent dans toutes les cohortes. La minéralisation à l’imagerie par résonance magnétique était moins fréquente dans les cohortes asiatique et moyenne-orientale que dans les autres. Par contre, l’atrophie cérébrale ou cérébelleuse était moins fréquente dans la cohorte asiatique. Le variant faux-sens homozygote (c.2222G>A,p.R741Q) était fréquent dans les cohortes indienne et moyenne-orientale, tandis que le variant homozygote/hétérozygote composé (c.991G > T, p.D331Y) était le plus fréquent dans la cohorte asiatique. Le variant c.991G > T (p.D331Y) était associé à des phénotypes cliniques et de neuro-imagerie plutôt légers et le variant c.2222G>A,p.R741Q, à un phénotype relativement grave.
La neurodégénérescence tardive présente différents phénotypes. Des différences phénotypiques ont été relevées entre les groupes ethniques; il en va de même pour l’imagerie entre les cohortes.
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Adult-Onset PLA2G6-Associated Neurodegeneration (PLAN): A Clinical, Imaging and Genetic Profile Review
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