Biallelic pathogenic variants of PARS2 cause developmental and epileptic encephalopathy with spike-and-wave activation in sleep.

Autor: Licchetta L; IRCCS Istituto delle Scienze Neurologiche di Bologna, Full member of the European Reference Network EpiCARE Bologna, Bologna, Italy., Di Giorgi L; IRCCS Istituto delle Scienze Neurologiche di Bologna, Full member of the European Reference Network EpiCARE Bologna, Bologna, Italy.; Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy., Santucci M; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Taruffi L; IRCCS Istituto delle Scienze Neurologiche di Bologna, Full member of the European Reference Network EpiCARE Bologna, Bologna, Italy., Stipa C; IRCCS Istituto delle Scienze Neurologiche di Bologna, Full member of the European Reference Network EpiCARE Bologna, Bologna, Italy., Minardi R; IRCCS Istituto delle Scienze Neurologiche di Bologna, Full member of the European Reference Network EpiCARE Bologna, Bologna, Italy., Carelli V; IRCCS Istituto delle Scienze Neurologiche di Bologna, Full member of the European Reference Network EpiCARE Bologna, Bologna, Italy.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Bisulli F; IRCCS Istituto delle Scienze Neurologiche di Bologna, Full member of the European Reference Network EpiCARE Bologna, Bologna, Italy.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2024 Jan; Vol. 12 (1), pp. e2311. Date of Electronic Publication: 2023 Dec 13.
DOI: 10.1002/mgg3.2311
Abstrakt: Background: Biallelic pathogenic variants in the mitochondrial prolyl-tRNA synthetase 2 gene (PARS2, OMIM * 612036) have been associated with Developmental and Epileptic Encephalopathy-75 (DEE-75, MIM #618437). This condition is typically characterized by early-onset refractory infantile spasms with hypsarrhythmia, intellectual disability, microcephaly, cerebral atrophy with hypomyelination, lactic acidemia, and cardiomyopathy. Most affected individuals do not survive beyond the age of 10 years.
Methods: We describe a patient with early-onset DEE, consistently showing an EEG pattern of Spike-and-Wave Activation in Sleep (SWAS) since childhood. The patient underwent extensive clinical, metabolic and genetic investigations, including whole exome sequencing (WES).
Results: WES analysis identified compound heterozygous variants in PARS2 that have been already reported as pathogenic. A literature review of PARS2-associated DEE, focusing mainly on the electroclinical phenotype, did not reveal the association of SWAS with pathogenic variants in PARS2. Notably, unlike previously reported cases with the same genotype, this patient had longer survival without cardiac involvement or lactic acidosis, suggesting potential genetic modifiers contributing to disease variability.
Conclusion: These findings widen the genetic heterogeneity of DEE-SWAS, including PARS2 as a causative gene in this syndromic entity, and highlight the importance of prolonged sleep EEG recording for the recognition of SWAS as a possible electroclinical evolution of PARS2-related DEE.
(© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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