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Expanding Phenotype Heterogeneity of Nars2 by Presenting Subdural Hematoma and Parenchymal Hemorrhage Publisher Pubmed



Khodaeian M1 ; Bitarafan F2 ; Garrousi F1 ; Sardehie EA1 ; Pak N3 ; Hosseinpour S4 ; Shakiba M5 ; Falah M6 ; Garshasbi M7 ; Tavasoli AR4, 8
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, DeNA Laboratory, Tehran, Iran
  2. 2. Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, 0450, Norway
  3. 3. Pediatric Radiology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pediatric Endocrinology and Metabolism, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  6. 6. ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Teheran, Iran
  8. 8. Department of Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ, United States

Source: Journal of Clinical Laboratory Analysis Published:2023


Abstract

Background: NARS2 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. Methods: The 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. Results: Here, 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. Conclusions: Our 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. © 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.
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