TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study.

DNA, Mitochondrial / genetics Humans Mitochondrial Diseases / complications Mutation / genetics Parkinson Disease / complications Parkinsonian Disorders / pathology Retrospective Studies

TWNK Parkinson's disease mitochondrial DNA parkinsonism twinkle

Journal

Movement disorders : official journal of the Movement Disorder Society

ISSN: 1531-8257

Titre abrégé: Mov Disord

Pays: United States

ID NLM: 8610688

Informations de publication

Date de publication:
09 2022

Historique:

revised: 17 05 2022

received: 23 02 2022

accepted: 30 05 2022

pubmed: 7 7 2022

medline: 16 9 2022

entrez: 6 7 2022

Statut: ppublish

Résumé

Parkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK. The aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK-related autosomal dominant progressive external ophthalmoplegia (TWNK-adPEO). Genomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK-adPEO patients with parkinsonism were retrospectively analyzed. Six of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK-adPEO patients, 5 (28%) had parkinsonism. We show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. © 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Sections du résumé

BACKGROUND

Parkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK.

OBJECTIVES

The aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK-related autosomal dominant progressive external ophthalmoplegia (TWNK-adPEO).

METHODS

Genomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK-adPEO patients with parkinsonism were retrospectively analyzed.

RESULTS

Six of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK-adPEO patients, 5 (28%) had parkinsonism.

CONCLUSIONS

We show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. © 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Identifiants

DOI: 10.1002/mds.29139 PMID: 35792653 PMC: PMC9544864

pubmed: 35792653

doi: 10.1002/mds.29139

pmc: PMC9544864

doi:

Substances chimiques

DNA, Mitochondrial 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1938-1943

Commentaires et corrections

Type : CommentIn

Informations de copyright

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