Expanding phenotype heterogeneity of NARS2 by presenting subdural hematoma and parenchymal hemorrhage

Abstract

AbstractBackgroundNARS2 encodes mitochondrial Asparaginyl‐tRNA Synthetase 2, which catalyzes the aminoacylation of tRNA‐Asn in the mitochondria. To date, 24 variants have been reported in NARS2 gene in 35 patients. The phenotypic variability of NARS2‐associated disorder is broad, ranging from neurodevelopmental disorders to hearing loss. In this study, we report some novel imaging findings in an Iranian patient suffering from epileptic encephalopathy, caused by a previously reported variant, c.500A > G; p.(His167Arg), in NARS2.MethodsThe spectrum of clinical manifestations of two Iranian patients was investigated and genetic analysis was performed by Whole‐exome sequencing (WES). Additionally, we also reviewed the literature and summarized the phenotypes of previously reported patients with variants in the NARS2 gene.ResultsHere, we present the phenotypic and genetic features of 2 unrelated Iranian infants presented with neurodevelopmental delay, seizures, hearing impairment, feeding problems, elevated serum lactate levels in addition to subdural hematoma and cerebral parenchymal hemorrhage in the brain magnetic resonance imaging (MRI) of one of the patients. Genetic analysis revealed a biallelic missense variant in NARS2: c.500A > G; p.(His167Arg). We described the subdural hematoma and cerebral parenchymal hemorrhage of the brain for the first time.ConclusionsOur study provides new clinical findings, subdural hematoma, and parenchymal hemorrhage, in NARS2‐related disorders. Our findings along with previous studies provide more evidence of the clinical presentation of the disease caused by pathogenic variants in NARS2. Expanding the clinical spectrum increases the diagnostic rate of molecular testing and improves the quality of counseling for at‐risk couples.