ArticleNeurology. Genetics2021
Mild Phenotype of Wolfram Syndrome Associated With a Common Pathogenic Variant Is Predicted by a Structural Model of Wolframin.
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Article in Neurology. Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
- The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher GenesInternational journal of molecular sciences · 2021Trial
- Consensus Recommendations for the Clinical Management of Wolfram syndrome Using a Delphi Method.medRxiv : the preprint server for health sciences · 2026Article
- Neutropenia Through Enhanced Neutrophil Apoptosis and Secondary Necrosis in Wolfram Syndrome 1Turkish journal of haematology : official journal of Turkish Society of Haematology · 2026Article
- Neonatal and Syndromic Forms of Diabetes.Current diabetes reports · 2025Review
- A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome.Diabetologia · 2025Article
- Expanding the spectrum of white matter abnormalities in Wolfram syndrome: a retrospective review.Frontiers in neurology · 2025Article
- Identification of a pathogenic founder variant in theFrontiers in pediatrics · 2025Article
- Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy.Scientific reports · 2024Article
- Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review.Brain sciences · 2023Article
- Genotype and Clinical Characteristics of Patients with Wolfram Syndrome and WFS1-related Disorders.medRxiv : the preprint server for health sciences · 2023Article
- Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders.Frontiers in genetics · 2023Article
- An Atypical Case of Late-Onset Wolfram Syndrome 1 without Diabetes Insipidus.International journal of environmental research and public health · 2022Article
- In-silico phenotype prediction by normal mode variant analysis in TUBB4A-related disease.Scientific reports · 2022Article
- Computational normal mode analysis accurately replicates the activity and specificity profiles of CRISPR-Cas9 and high-fidelity variants.Computational and structural biotechnology journal · 2022Article
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Authors and funding
14 authors at 1 institution in 1 country.
Adi Wilf-YarkoniNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Oded ShorNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Avi FellnerNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Mark Andrew HellmannNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Elon PrasNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Hagit YonathNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Shiri Shkedi-RafidNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Lina Basel-SalmonNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Lili BazakNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Ruth EliahouNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Lior GreenbaumNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Hadas Stiebel-KalishNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Felix BenningerNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.ORCID 0000-0003-3097-4693
Yael GoldbergNeuro-Immunology Unit (A.W-.Y., M.A.H.), Department of Neurology (O.S., A.F., F.B.), Department of Radiology (R.E.), and Neuro-Ophthalmology Unit, Department of Ophthalmology (H.S.K.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine (O.S., E.P., H.Y., L.B.-S., L.G., H.S.-K., F.B., Y.G.), Tel Aviv University, Tel Aviv, Israel; The Raphael Recanati Genetic Institute (A.F., Y.G., L.B.-S., L.B.), Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel; The Danek Gertner Institute of Human Genetics (E.P., H.Y., L.G.), Sheba Medical Center, Tel Hashomer, Israel; The Joseph Sagol Neuroscience Center (E.P., L.G.), Sheba Medical Center, Tel Hashomer, Israel; Department of Internal Medicine A (H.Y.), Sheba Medical Center, Tel Hashomer, Israel; Department of Genetics and Faculty of Medicine (S.S.-R.), Hadassah-Hebrew University Hospital, Jerusalem, Israel; Felsenstein Medical Research Center (O.S., L.B.-S., F.B.), Petach Tikva, Israel.
Hebrew University of Jerusalem · IL
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo describe the
methodsThe clinical, laboratory, and genetic features of 8 homozygotes were collected. A model of the wolframin protein was constructed, and NMA was used to simulate the effect of the variant on protein thermodynamics.
resultsMean age at Wolfram syndrome (WS) diagnosis among homozygotes was 30 years; diabetes (7/8) was diagnosed at mean age 19 years (15-21 years), and bilateral optic atrophy (with MRI evidence of optic/chiasm atrophy) (6/8) at mean age 29 years (15-48 years). The oldest patient (62 years) also had gait difficulties, memory problems, parietal and cerebellar atrophy, and white matter hyperintense lesions. All retained functional vision with independent ambulation and self-care; none had diabetes insipidus or hearing loss. The p.R558C variant caused less impairment of protein entropy than WFS1 variants associated with a more severe phenotype.
conclusionsThe p.R558C variant causes a milder, late-onset phenotype of WS. We report a structural model of wolframin protein based on empirical functional studies and use NMA modeling to show a genotype-phenotype correlation across all homozygotes. Clinicians should be alert to this condition in patients with juvenile diabetes and patients of any age with a combination of diabetes and optic atrophy. Computational NMA has potential benefit for prediction of the genotype-phenotype relationship.
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