Hearing lossGene: FDXR
Comment on list classification: There are 3 cases where hearing loss is reported as the first symptom, although there are other cases in which variants in this gene do not result in hearing loss, or hearing loss after an optic phenotype. Rating amber for now until this gene can be reviewed by the GMS.
Created: 8 Sep 2020, 7:16 p.m. | Last Modified: 8 Sep 2020, 8:38 p.m.
Panel Version: 2.53
Associated with Auditory neuropathy and optic atrophy #617717 (AR) in OMIM.
PMID: 28965846 - Paul et al 2017 - report 8 individuals from 4 families from Tunisia, Algeria, France and Russia/Azerbaijan. All were affected by auditory neuropathy and optic atrophy with first onset before age 20. In 4/8 individuals from 3 families hearing loss was the first symptom. In all cases biallelic (homozygous or compound het) variants in FDXR were found (exome sequencing in family 1, direct sequencing in the other 3 families). The variants segregated with the phenotype in family 1 (homozygous variant). Parental DNA was not available for other families. No FDXR variants were found in 86 other patients with different types of hearing loss. FDXR encodes a mitochondrial NADPH. FDXR levels were decreased in fibroblasts derived from patients in two of the families. Functional studies suggest a defect in iron homeostasis. Yeast studies showed that some of the FDXR variants failed to rescue growth defects in FDXR ortholog arh1 knockouts, but wildtype FDXR was able to rescue the defect.
PMID: 29040572 (Peng et al 2017) - report 17 individuals from 13 unrelated families with recessive mutations in FDXR. The core clinical features were optic atrophy, ataxia, and hypotonia but hearing loss was also noted as a less common phenotype.
Note, other cases reported with variants FDXR but no hearing loss phenotype e.g. PMID: 30250212 (Slone et al, 2018)
Created: 8 Sep 2020, 4:37 p.m. | Last Modified: 8 Sep 2020, 7:14 p.m.
Panel Version: 2.52
Auditory neuropathy and optic atrophy 617717
8 individuals from 4 unrelated families reported, onset of symptoms in first/second decades.
Sources: Expert list
Created: 29 Jan 2020, 12:41 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Auditory neuropathy and optic atrophy, MIM# 617717
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review tag was added to gene: FDXR.
Gene: fdxr has been classified as Amber List (Moderate Evidence).
gene: FDXR was added gene: FDXR was added to Hearing loss. Sources: Expert list Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FDXR were set to 28965846 Phenotypes for gene: FDXR were set to Auditory neuropathy and optic atrophy, MIM# 617717 Review for gene: FDXR was set to GREEN gene: FDXR was marked as current diagnostic