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PRKN-Gene-Related Parkinsonism: An Experience from a Tertiary Centre and Literature Review of Asian Cohort

Published online by Cambridge University Press:  16 January 2025

Vikram V. Holla Open the ORCID record for Vikram V. Holla [Opens in a new window] ,
Debjyoti Dhar Open the ORCID record for Debjyoti Dhar [Opens in a new window] ,
Prashant Phulpagar Open the ORCID record for Prashant Phulpagar [Opens in a new window] ,
M.M. Samim Open the ORCID record for M.M. Samim [Opens in a new window] ,
Sneha D. Kamath Open the ORCID record for Sneha D. Kamath [Opens in a new window] ,
Nitish Kamble Open the ORCID record for Nitish Kamble [Opens in a new window] ,
Babylakshmi Muthusamy Open the ORCID record for Babylakshmi Muthusamy [Opens in a new window] ,
Ravi Yadav Open the ORCID record for Ravi Yadav [Opens in a new window]  and
Pramod Kumar Pal Open the ORCID record for Pramod Kumar Pal [Opens in a new window]
Vikram V. Holla
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
Debjyoti Dhar
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
Prashant Phulpagar
Affiliation:
Institute of Bioinformatics, International Technology Park, Bangalore, India Manipal Academy of Higher Education, Manipal, Karnataka, India
M.M. Samim
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
Sneha D. Kamath
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
Nitish Kamble
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
Babylakshmi Muthusamy
Affiliation:
Institute of Bioinformatics, International Technology Park, Bangalore, India Department of Medical Genetics, Kasturba Medical CollegeManipal Academy of Higher Education, Manipal, India
Ravi Yadav
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
Pramod Kumar Pal*
Affiliation:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India
*
Corresponding authors: Pramod K. Pal; Email: palpramod@hotmail.com
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Abstract:

Background:

PRKN-related parkinsonism represents one of the most common types of genetically determined Parkinson’s disease (PD). However, the literature among the Asian ethnicity, particularly in the Indian context, is limited.

Objective:

To study the clinico-genetic profile of patients with PRKN-related parkinsonism and to review the previously reported cases of PRKN-related parkinsonism from Asia.

Methods:

A retrospective chart review from a tertiary neurology centre of patients with genetically confirmed PRKN-related parkinsonism. Additionally, we consolidated the Asian cohort from a detailed systematic review of the literature. We utilised the Movement Disorders Society gene cohort for comparison with the world literature.

Results:

We recruited 16 cases (males = 10, Early onset Parkinson disease (21 to <50 years age at onset)) of PRKN-related parkinsonism with a median age at onset of 28.5 years (range 14–46). Symptoms included parkinsonism (n = 15), dystonia (n = 10), postural instability (n = 7), freezing of gait (n = 5) and non-motor symptoms (NMS) (n = 10). The commonest symptom at onset was tremors (n = 10). Levodopa responsiveness was observed in all cases with drug-induced dyskinesia in eight (50%). Thirteen cases were homozygous, while three were compound heterozygotes, resulting in 19 variants (novel = 5). Exon deletion was the most common (n = 12). The extended Asian cohort comprising 294 cases had a high prevalence of EOPD (n = 186/257, 72.4%) and familial cases (n = 166/252, 65.9%). Deletion/duplication was the common mutation detected (n = 215, 73.1%). The presumed familial cases had a significantly higher frequency of rest tremors, bradykinesia, postural instability, NMS, dyskinesia and sleep disorders.

Conclusion:

This largest single-centre study from India adds 16 new cases and five novel variants to PRKN literature. In addition, it consolidates the Asian cohort of PRKN elucidating its unique attributes.

Résumé :

RÉSUMÉ :

Le parkinsonisme lié au gène PRKN : expérience au sein d’un centre de neurologie tertiaire et revue de la littérature portant sur une cohorte de patients d’origine asiatique

Contexte :

Bien que le parkinsonisme lié au gène PRKN (PARK-PRKN) représente l’un des types les plus courants de la maladie de Parkinson (MP) d’origine génétique, la littérature scientifique concernant des patients asiatiques, en particulier dans le contexte indien, est moins bien définie.

Objectif :

Étudier le profil clinique et génétique des patients atteints de PARK-PRKN et passer en revue les cas de PARK-PRKN précédemment rapportés en Asie.

Méthodes :

Conduire un examen rétrospectif des dossiers de patients d’un centre de neurologie tertiaire présentant un PARK-PRKN confirmé génétiquement. En outre, nous avons consolidé cette cohorte de patients asiatiques à partir d’une revue systématique et détaillée de la littérature. Nous avons notamment utilisé la cohorte génétique de la Movement Disorders Society (MDS) pour la comparer à la littérature mondiale.

Résultats :

Nous avons retenu 16 cas de PARK-PRKN (hommes = 10, FPMP-13) dont l’âge médian d’apparition chez les patients était de 28,5 ans (intervalle 14-46). Les symptômes comprenaient le parkinsonisme (n = 15), la dystonie (n = 10), l’instabilité posturale (n = 7), le gel de la marche (n = 5) et des symptômes non moteurs (n = 10). Le symptôme le plus fréquent au début de la maladie était les tremblements (n = 10). Une réponse à un traitement de lévodopa a été observée dans tous les cas, avec une dyskinésie induite par le médicament dans 8 cas (50 %). Fait à noter, 13 cas étaient homozygotes et 3 autres étaient des hétérozygotes composés, ce qui a donné lieu à 19 variantes (nouvelle = 5). La délétion d’exon était la plus fréquente (n = 12). De plus, la cohorte asiatique élargie, composée de 294 cas, présentait une prévalence élevée de la forme précoce de la maladie (n = 186/257, 72,4 %) et de cas familiaux (n = 166/252, 65,9 %). La délétion/duplication était la mutation la plus fréquemment détectée (n = 215, 73,1 %). Enfin, des cas présumés familiaux présentaient une fréquence significativement plus élevée de tremblements au repos, de bradykinésie, d’instabilité posturale, de symptômes non moteurs, de dyskinésie et de troubles du sommeil.

Conclusion :

Cette étude monocentrique la plus importante réalisée en Inde ajoute 16 nouveaux cas et 5 nouvelles variantes à la littérature portant sur le PARK-PRKN. En outre, elle consolide la cohorte de patients asiatiques atteints de PARK-PRKN en élucidant ses caractéristiques uniques.

Keywords

Asiaearly-onset Parkinson’s diseaseparkinPRKNparkinsonism

Information

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 52 , Issue 5 , September 2025 , pp. 829 - 840
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

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Footnotes

*

Contributed equally

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