ArticleAmerican journal of medical genetics. Part A2011
Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.
Article in American journal of medical genetics. Part A, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.
- WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome.BMC medical genomics · 2023Pooled it
- The Impact of Mutations in Wolframin on Psychiatric Disorders.Frontiers in pediatrics · 2021Pooled it
- Consensus Recommendations for the Clinical Management of Wolfram syndrome Using a Delphi Method.medRxiv : the preprint server for health sciences · 2026Article
- Genotype-Based Severity Scoring System in Wolfram Syndrome: Correlation with Onset of Cardinal Symptoms andmedRxiv : the preprint server for health sciences · 2026Article
- Natural history of 15 patients with autosomal dominant WFS1 pathogenic variants associated with sensorineural hearing loss and optic atrophy.Orphanet journal of rare diseases · 2026Article
- WFS1 gene delivery rescues visual function in a mouse model of Wolfram syndrome.Acta neuropathologica communications · 2026Article
- Genotype-based severity scoring system in Wolfram Syndrome: correlation with onset of cardinal symptoms andFrontiers in genetics · 2026Article
- Genomic Insights into Unspecified Monogenic Forms of Diabetes and Their Associated Comorbidities: Implication for Treatment.Current issues in molecular biology · 2025Article
- Next-Generation Sequencing to Detect Mutations for the Molecular Diagnosis of Auditory Neuropathy Spectrum Disorder in a Chinese Series.The journal of international advanced otology · 2025Article
- SID/SIEDP expert consensus on optimizing clinical strategies for early detection and management of wolfram syndrome.Journal of endocrinological investigation · 2025Review
- The Heterozygous p.A684V Variant in theGenes · 2025Article
- Monogenic diabetes: the role of mitochondrial dysfunction and endoplasmic reticulum stress.Frontiers in clinical diabetes and healthcare · 2025Review
- Topology ofPediatric diabetes · 2025Article
- Article
- Clinical Characteristics and Audiological Profiles of Patients with Pathogenic Variants ofJournal of clinical medicine · 2024Article
- Review
- Multifaceted Roles of AFG3L2, a Mitochondrial ATPase in Relation to Neurological Disorders.Molecular neurobiology · 2024Review
- Genetic Etiology of Nonsyndromic Hearing Loss in Hungarian Patients.International journal of molecular sciences · 2023Article
- Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.International journal of molecular sciences · 2023Review
- Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder.Journal of clinical medicine · 2023Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 10 institutions in 5 countries.
Funding
Abstract
Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in WFS1. In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare, and almost exclusively attributed to mutations in the Optic Atrophy-1 gene (OPA1), most commonly the p.R445H mutation. We present eight probands and their families from the US, Sweden, and UK with OA and SNHL, whom we analyzed for mutations in OPA1 and WFS1. Among these families, we found three heterozygous missense mutations in WFS1 segregating with OA and SNHL: p.A684V (six families), and two novel mutations, p.G780S and p.D797Y, all involving evolutionarily conserved amino acids and absent from 298 control chromosomes. Importantly, none of these families harbored the OPA1 p.R445H mutation. No mitochondrial DNA deletions were detected in muscle from one p.A684V patient analyzed. Finally, wolframin p.A684V mutant ectopically expressed in HEK cells showed reduced protein levels compared to wild-type wolframin, strongly indicating that the mutation is disease-causing. Our data support OA and SNHL as a phenotype caused by dominant mutations in WFS1 in these additional eight families. Importantly, our data provide the first evidence that a single, recurrent mutation in WFS1, p.A684V, may be a common cause of ADOA and SNHL, similar to the role played by the p.R445H mutation in OPA1. Our findings suggest that patients who are heterozygous for WFS1 missense mutations should be carefully clinically examined for OA and other manifestations of Wolfram syndrome.
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