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| Monogenic hearing loss v2.230 | FDXR | Eleanor Williams Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Auditory neuropathy and optic atrophy, OMIM:617717 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.229 | FDXR | Eleanor Williams Tag for-review was removed from gene: FDXR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.221 | FDXR | Eleanor Williams commented on gene: FDXR: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.220 | FDXR |
Eleanor Williams Source Expert Review Green was added to FDXR. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Monogenic hearing loss v2.53 | FDXR | Eleanor Williams edited their review of gene: FDXR: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.53 | FDXR | Eleanor Williams Tag for-review tag was added to gene: FDXR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.53 | FDXR | Eleanor Williams changed review comment from: 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.; to: 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.53 | FDXR | Eleanor Williams Classified gene: FDXR as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.53 | FDXR | Eleanor Williams Added comment: 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.53 | FDXR | Eleanor Williams Gene: fdxr has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.52 | FDXR |
Eleanor Williams changed review comment from: 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 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) ; to: 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) |
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| Monogenic hearing loss v2.52 | FDXR |
Eleanor Williams changed review comment from: 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 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.; to: 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 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) |
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| Monogenic hearing loss v2.52 | FDXR | Eleanor Williams reviewed gene: FDXR: Rating: ; Mode of pathogenicity: None; Publications: 28965846; Phenotypes: Auditory neuropathy and optic atrophy 617717; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.4 | FDXR |
Zornitza Stark 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 Added comment: 8 individuals from 4 unrelated families reported, onset of symptoms in first/second decades. Sources: Expert list |
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