The Expanding Phenotypical Spectrum of WARS2 -Related Disorder : Four Novel Cases with a Common Recurrent Variant
Pauly, Martje G. (University Hospital Schleswig Holstein)
Korenke, G. Christoph (University Children's Hospital)
Diaw, Sokhna Haissatou (University of Luebeck)
Grözinger, Anne (University of Luebeck)
Cazurro-Gutiérrez, Ana Laura (Hospital Universitari Vall d'Hebron)
Pérez-Dueñas, Belén (Hospital Universitari Vall d'Hebron)
González, Victoria (Hospital Universitari Vall d'Hebron)
Macaya Ruiz, Alfons (Hospital Universitari Vall d'Hebron)
Serrano Antón, Ana Teresa (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Peterlin, Borut (University Medical Centre Ljubljana)
Božović, Ivana Babić (University Medical Centre Ljubljana)
Maver, Aleš (University Medical Centre Ljubljana)
Münchau, Alexander (University of Luebeck)
Lohmann, Katja (University of Luebeck)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	Biallelic variants in the mitochondrial form of the tryptophanyl-tRNA synthetases (WARS2) can cause a neurodevelopmental disorder with movement disorders including early-onset tremor-parkinsonism syndrome. Here, we describe four new patients, who all presented at a young age with a tremor-parkinsonism syndrome and responded well to levodopa. All patients carry the same recurrent, hypomorphic missense variant (NM_015836. 4: c. 37T>G; p. Trp13Gly) either together with a previously described truncating variant (NM_015836. 4: c. 797Cdel; p. Pro266ArgfsTer10), a novel truncating variant (NM_015836. 4: c. 346C>T; p. Gln116Ter), a novel canonical splice site variant (NM_015836. 4: c. 349-1G>A), or a novel missense variant (NM_015836. 4: c. 475A>C, p. Thr159Pro). We investigated the mitochondrial function in patients and found increased levels of mitochondrially encoded cytochrome C Oxidase II as part of the mitochondrial respiratory chain as well as decreased mitochondrial integrity and branching. Finally, we conducted a literature review and here summarize the broad phenotypical spectrum of reported WARS2 -related disorders. In conclusion, WARS2 -related disorders are diagnostically challenging diseases due to the broad phenotypic spectrum and the disease relevance of a relatively common missense change that is often filtered out in a diagnostic setting since it occurs in ~0. 5% of the general European population.
Ajuts:	Instituto de Salud Carlos III PI21/00248
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Levodopa ; Parkinsonism ; Tremor ; WARS2
Publicat a:	Genes, Vol. 14 (march 2023) , ISSN 2073-4425

DOI: 10.3390/genes14040822
PMID: 37107582

11 p, 1.6 MB

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