WARS2 mutations cause dopa-responsive early-onset parkinsonism
and progressive myoclonus ataxia

J 2022

WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia

SKORVANEK, Matej; Irena REKTOROVÁ; Wim MANDEMAKERS; Matias WAGNER; Robert STEINFELD et. al.

Základní údaje

Originální název

WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia

Autoři

SKORVANEK, Matej (garant); Irena REKTOROVÁ (203 Česká republika, domácí); Wim MANDEMAKERS; Matias WAGNER; Robert STEINFELD; Laura OREC; Vladimir HAN; Petra PAVELEKOVA; Alexandra LACKOVA; Kristina KULCSAROVA; Miriam OSTROZOVICOVA; Zuzana GDOVINOVA; Barbara PLECKO; Theresa BRUNET; Riccardo BERUTTI; Demy J S KUIPERS; Valerie BOUMEESTER; Petra HAVRANKOVA; M A J TIJSSEN; Rauan KAIYRZHANOV; Mie RIZIG; Henry HOULDEN; Juliane WINKELMANN; Vincenzo BONIFATI; Michael ZECH a Robert JECH

Vydání

PARKINSONISM & RELATED DISORDERS, OXFORD, ELSEVIER SCI LTD, 2022, 1353-8020

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30210 Clinical neurology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.100

Kód RIV

RIV/00216224:14110/22:00128075

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1016/j.parkreldis.2021.11.030

UT WoS

000748987300009

EID Scopus

2-s2.0-85120773777

Klíčová slova anglicky

WARS2; Early onset parkinsonism; Progressive myoclonus ataxia; Whole exome sequencing

Štítky

14110127, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 2. 2023 14:12, Mgr. Tereza Miškechová

Anotace

V originále

Introduction: Sixteen subjects with biallelic WARS2 variants encoding the tryptophanyl mitochondrial aminoacyl-tRNA synthetase, presenting with a neonatal- or infantile-onset mitochondrial disease, have been reported to date. Here we present six novel cases with WARS2-related diseases and expand the spectrum to later onset phenotypes including dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia. Methods: Six individuals from four families underwent whole-exome sequencing within research and diagnostic settings. Following the identification of a genetic defect, in-depth phenotyping and protein expression studies were performed. Results: A relatively common (gnomAD MAF = 0.0033) pathogenic p.(Trp13Gly) missense variant in WARS2 was detected in trans in all six affected individuals in combination with different pathogenic alleles (exon 2 deletion in family 1; p.(Leu100del) in family 2; p.(Gly50Asp) in family 3; and p.(Glu208*) in family 4). Two subjects presented with action tremor around age 10-12 years and developed tremor-dominant parkinsonism with prominent neuropsychiatric features later in their 20s. Two subjects presented with a progressive myoclonusataxia dominant phenotype. One subject presented with spasticity, choreo-dystonia, myoclonus, and speech problems. One subject presented with speech problems, ataxia, and tremor. Western blotting analyses in patientderived fibroblasts showed a markedly decreased expression of the full-length WARS2 protein in both subjects carrying p.(Trp13Gly) and an exon-2 deletion in compound heterozygosity. Conclusions: This study expands the spectrum of the disease to later onset phenotypes of early-onset tremordominant parkinsonism and progressive myoclonus-ataxia phenotypes.

Citovat

SKORVANEK, Matej; Irena REKTOROVÁ; Wim MANDEMAKERS; Matias WAGNER; Robert STEINFELD; Laura OREC; Vladimir HAN; Petra PAVELEKOVA; Alexandra LACKOVA; Kristina KULCSAROVA; Miriam OSTROZOVICOVA; Zuzana GDOVINOVA; Barbara PLECKO; Theresa BRUNET; Riccardo BERUTTI; Demy J S KUIPERS; Valerie BOUMEESTER; Petra HAVRANKOVA; M A J TIJSSEN; Rauan KAIYRZHANOV; Mie RIZIG; Henry HOULDEN; Juliane WINKELMANN; Vincenzo BONIFATI; Michael ZECH a Robert JECH. WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia. PARKINSONISM & RELATED DISORDERS. OXFORD: ELSEVIER SCI LTD, 2022, roč. 94, January 2022, s. 54-61. ISSN 1353-8020. Dostupné z: https://dx.doi.org/10.1016/j.parkreldis.2021.11.030.

@article{2247546,
   author = {Skorvanek, Matej and Rektorová, Irena and Mandemakers, Wim and Wagner, Matias and Steinfeld, Robert and Orec, Laura and Han, Vladimir and Pavelekova, Petra and Lackova, Alexandra and Kulcsarova, Kristina and Ostrozovicova, Miriam and Gdovinova, Zuzana and Plecko, Barbara and Brunet, Theresa and Berutti, Riccardo and Kuipers, Demy J S and Boumeester, Valerie and Havrankova, Petra and Tijssen, M A J and Kaiyrzhanov, Rauan and Rizig, Mie and Houlden, Henry and Winkelmann, Juliane and Bonifati, Vincenzo and Zech, Michael and Jech, Robert},
   article_location = {OXFORD},
   article_number = {January 2022},
   doi = {http://dx.doi.org/10.1016/j.parkreldis.2021.11.030},
   keywords = {WARS2; Early onset parkinsonism; Progressive myoclonus ataxia; Whole exome sequencing},
   language = {eng},
   issn = {1353-8020},
   journal = {PARKINSONISM & RELATED DISORDERS},
   title = {WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia},
   url = {https://www.sciencedirect.com/science/article/pii/S1353802021004375?via%3Dihub},
   volume = {94},
   year = {2022}
}

TY  - JOUR
ID  - 2247546
AU  - Skorvanek, Matej - Rektorová, Irena - Mandemakers, Wim - Wagner, Matias - Steinfeld, Robert - Orec, Laura - Han, Vladimir - Pavelekova, Petra - Lackova, Alexandra - Kulcsarova, Kristina - Ostrozovicova, Miriam - Gdovinova, Zuzana - Plecko, Barbara - Brunet, Theresa - Berutti, Riccardo - Kuipers, Demy J S - Boumeester, Valerie - Havrankova, Petra - Tijssen, M A J - Kaiyrzhanov, Rauan - Rizig, Mie - Houlden, Henry - Winkelmann, Juliane - Bonifati, Vincenzo - Zech, Michael - Jech, Robert
PY  - 2022
TI  - WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia
JF  - PARKINSONISM & RELATED DISORDERS
VL  - 94
IS  - January 2022
SP  - 54-61
EP  - 54-61
PB  - ELSEVIER SCI LTD
SN  - 13538020
KW  - WARS2
KW  - Early onset parkinsonism
KW  - Progressive myoclonus ataxia
KW  - Whole exome sequencing
UR  - https://www.sciencedirect.com/science/article/pii/S1353802021004375?via%3Dihub
N2  - Introduction: Sixteen subjects with biallelic WARS2 variants encoding the tryptophanyl mitochondrial aminoacyl-tRNA synthetase, presenting with a neonatal- or infantile-onset mitochondrial disease, have been reported to date. Here we present six novel cases with WARS2-related diseases and expand the spectrum to later onset phenotypes including dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia. Methods: Six individuals from four families underwent whole-exome sequencing within research and diagnostic settings. Following the identification of a genetic defect, in-depth phenotyping and protein expression studies were performed. Results: A relatively common (gnomAD MAF = 0.0033) pathogenic p.(Trp13Gly) missense variant in WARS2 was detected in trans in all six affected individuals in combination with different pathogenic alleles (exon 2 deletion in family 1; p.(Leu100del) in family 2; p.(Gly50Asp) in family 3; and p.(Glu208*) in family 4). Two subjects presented with action tremor around age 10-12 years and developed tremor-dominant parkinsonism with prominent neuropsychiatric features later in their 20s. Two subjects presented with a progressive myoclonusataxia dominant phenotype. One subject presented with spasticity, choreo-dystonia, myoclonus, and speech problems. One subject presented with speech problems, ataxia, and tremor. Western blotting analyses in patientderived fibroblasts showed a markedly decreased expression of the full-length WARS2 protein in both subjects carrying p.(Trp13Gly) and an exon-2 deletion in compound heterozygosity. Conclusions: This study expands the spectrum of the disease to later onset phenotypes of early-onset tremordominant parkinsonism and progressive myoclonus-ataxia phenotypes.
ER  -

SKORVANEK, Matej; Irena REKTOROVÁ; Wim MANDEMAKERS; Matias WAGNER; Robert STEINFELD; Laura OREC; Vladimir HAN; Petra PAVELEKOVA; Alexandra LACKOVA; Kristina KULCSAROVA; Miriam OSTROZOVICOVA; Zuzana GDOVINOVA; Barbara PLECKO; Theresa BRUNET; Riccardo BERUTTI; Demy J S KUIPERS; Valerie BOUMEESTER; Petra HAVRANKOVA; M A J TIJSSEN; Rauan KAIYRZHANOV; Mie RIZIG; Henry HOULDEN; Juliane WINKELMANN; Vincenzo BONIFATI; Michael ZECH a Robert JECH. WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia. \textit{PARKINSONISM \&{} RELATED DISORDERS}. OXFORD: ELSEVIER SCI LTD, 2022, roč.~94, January 2022, s.~54-61. ISSN~1353-8020. Dostupné z: https://dx.doi.org/10.1016/j.parkreldis.2021.11.030.

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