Hearing lossGene: NARS2
Only one family described with isolated deafness; however, deafness is also part of the phenotype of the multi-system mitochondrial disorder associated with this gene, and it is difficult to know in what proportion of patients it may initially present with limited features such as deafness.
Created: 2 Jan 2020, 5:09 a.m. | Last Modified: 2 Jan 2020, 5:09 a.m.
Panel Version: 2.4
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Deafness, autosomal recessive 94, MIM#618434; Combined oxidative phosphorylation deficiency 24, MIM#616239
Variants in this GENE are reported as part of current diagnostic practice
Included in our current panel, no class 4 or 5 variants identified. One report of a homozygous missense variant associated with non-syndromic deafness (Simon et al 2015 PMID 25807530). Large consanguineous family 6 affected members all homozygous.
Created: 17 Feb 2019, 4:35 p.m.
Comment on list classification: Changing the rating from red to amber for NARS2. Only one family with non-syndromic deafness, but several with deafness in conjunction with other clinical features. This gene should be reviewed at the next major GMS update to decide whether it would be appropriate for the panel as a green gene.
Created: 24 Nov 2020, 7:58 p.m. | Last Modified: 24 Nov 2020, 7:59 p.m.
Panel Version: 2.116
PMID: 25807530 - Simon et al 2015 - report 2 unrelated families with 3 different variants in NARS2. One family is segregating nonsyndromic hearing loss (DFNB94) and another with Leigh syndrome. In the family with Leigh syndrome two affected children failed the newborn hearing test.
PMID: 28077841 - Mizuguchi et al 2017 - report 4 individuals from 3 families with homozygous or compound het variants in NARS2 found by WES. All had hearing impairment (detected <2 years of age) among other clinical features including seizures and hypotonia.
PMID: 30327238 - Seaver et al 2018 - report two infant brothers who presented with focal status epilepticus that progressed to lethal epileptic encephalopathy. Compound het missense variants found by WES in NARS2. The younger brother failed the newborn hearing screen.
PMID: 25385316 - Vanlander et al 2015 - report 2 siblings born to consanguineous parents in which a homozygous missense mutation (c.822G>C) was found in NARS2). One sibling had mild intellectual disability and epilepsy in childhood, whereas the other had severe myopathy. Hearing loss NOT reported.
Created: 24 Nov 2020, 7:56 p.m. | Last Modified: 24 Nov 2020, 7:56 p.m.
Panel Version: 2.115
Added at suggestion of Emma Ashton, GOSH
Sources: Expert list
Created: 17 Feb 2019, 4:33 p.m.
Mode of inheritance
Tag for-review tag was added to gene: NARS2.
Gene: nars2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: NARS2 were changed from to Deafness, autosomal recessive 94 OMIM:618434; Combined oxidative phosphorylation deficiency 24 OMIM:616239; deafness, autosomal recessive 94 MONDO:0032749; combined oxidative phosphorylation defect type 24 MONDO:0014547
Publications for gene: NARS2 were set to 25807530
Publications for gene: NARS2 were set to
Mode of inheritance for gene: NARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
gene: NARS2 was added gene: NARS2 was added to Hearing loss. Sources: Expert list Mode of inheritance for gene: NARS2 was set to Unknown