Bilateral Nonsyndromic Sensorineural Hearing Loss Caused by a NARS2 Mutation

Abstract

Mitochondrial diseases disrupt the process of energy generation by the mitochondria, leading to manifestations that can affect almost any organ in the body. Although various possible clinical phenotypes can result, neurological and neuromuscular affection is most frequently encountered. NARS2 encodes an enzyme responsible for the conjugation of asparagine to its cognate mitochondrial transfer ribonucleic acid (tRNA) molecule, representing an essential step necessary for effective mitochondrial protein synthesis. As such, mutations in this gene can lead to poor mitochondrial gene expression and, consequently, poor energy output resulting in disease. Pathogenic variants in NARS2 have been known to cause neurodegenerative and myopathic syndromes in combined oxidative phosphorylation deficiency 24 (COXPD24). However, nonsyndromic autosomal recessive deafness 94 (DFNB94), with which only one family is known to be affected, has also been reported concerning NARS2. Our report demonstrates the association of a new pathogenic variant in mitochondrial asparaginyl-tRNA synthetase (NARS2) with nonsyndromic sensorineural hearing loss, thus confirming biallelic mutations in NARS2 as a cause of nonsyndromic deafness.

Case Report: A new case of YARS1-associated autosomal recessive disorder with compound heterozygous and concurrent 47, XXY

“…Additionally, the paternal grandfather also contends with hearing loss. Notably, hearing impairment is a common feature in other tRNA synthetase mutation disorders, such as LARS2, which leads to Perrault syndrome ( 18 ), and NARS2, associated with nonsyndromic sensorineural hearing loss ( 19 ). This suggests a potential link between the YARS1 p.Arg367Trp pathogenic variant and hearing impairment, though the precise underlying mechanism remains unclear.…”

Progressive Mitochondrial Encephalopathy Due to the Novel Compound Heterozygous Variants c.182C>T and c.446A>AG in NARS2: A Case Report

“…Myoclonus, diabetes, spasticity, lactic acidosis, and microcephalus have been reported less frequently (Table 1) [1]. Some of the phenotypic features can occur in isolation, such as hearing loss or epilepsy [3][4][5][6][7]. With early onset in infancy, patients often suffer from growth retardation, intractable epilepsy, and hearing loss [3,4].…”

“…NARS2 variants cause a combined oxidative phosphorylation deficiency-24 (COXPD24) [3]. Biallelic variants in NARS2 cause mitochondrial disorders (MIDs) with a broad phenotypic spectrum [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The following case report describes a patient with MID due to a novel compound heterozygous variant in NARS2 that phenotypically manifested only in the brain.…”

Novel NARS2 variants in a patient with early-onset status epilepticus: case study and literature review

“…Up to now, only 30 variants in NARS2 gene have been reported, and the exact genotype-phenotype correlation is not clear. The number of case reports related NARS2 de ciency increased gradually 3,[5][6][7]9,[22][23][24] .…”