The phenotypic variability and natural history of NARS2 associated disease

• DOI: 10.1016/j.ejpn.2021.01.012
• Publication Date: 2021-02-05T17:54:52Z
• Authors: Kalliopi Sofou; Gittan Kollberg; Carola Hedberg-Ol...; Anders Oldfors
• Keywords: Male; 0301 basic medicine; Genotype; Hearing Loss, Sensorineural; Siblings; Aspartate-tRNA Ligase; Homozygote; Infant; 3. Good health; 03 medical and health sciences; Phenotype; Biological Variation, Population; Mitochondrial Encephalomyopathies; Child, Preschool; Mutation; Humans; Female; Child

The phenotypic variability of NARS2 associated disease is vast, yet not thoroughly explored. We present the and genetic features 2 siblings with early-onset mitochondrial encephalopathy due to pathogenic variant in NARS2, along results from a systematic literature review.To better delineate natural history disease.The clinical radiological phenotype, morphological biochemical investigations muscle biopsy as well postmortem investigations, where applicable, are presented. Genetic analysis was performed next-generation sequencing.Together these patients, we have diagnosed followed 3 Scandinavian patients same homozygous p. Pro214Leu who presented variable course. Another 14 variants were identified literature. found that sensorineural hearing impairment cardinal feature disease, either isolated or combination central nervous system disease. Early-onset shared Alpers Leigh syndrome characterized by more severe course poorer survival compared other phenotypes.NARS2 spectrum severity severe, infantile-onset, progressive mild, non-progressive without strong association between genotype outcome.