{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:11:32Z","timestamp":1760235092301,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wolfram syndrome is a rare autosomal recessive disorder characterized by optic atrophy and diabetes mellitus. Wolfram syndrome type 1 (WFS1) is caused by bi-allelic pathogenic variations in the wolframin gene. We described the first case of WFS1 due to a maternal inherited mutation with uniparental mero-isodisomy of chromosome 4. Diabetes mellitus was diagnosed at 11 years of age, with negative anti-beta cells antibodies. Blood glucose control was optimal with low insulin requirement. No pathogenic variations in the most frequent gene causative of maturity-onset diabetes of the young subtypes were detected. At 17.8 years old, a rapid reduction in visual acuity occurred. Genetic testing revealed the novel homozygous variant c.1369A&gt;G; p.Arg457Gly in the exon 8 of wolframin gene. It was detected in a heterozygous state only in the mother while the father showed a wild type sequence. In silico disease causing predictions performed by Polyphen2 classified it as \u201clikely damaging\u201d, while Mutation Tester and Sift suggested it was \u201cpolymorphism\u201d and \u201ctolerated\u201d, respectively. High resolution SNP-array analysis was suggestive of segmental uniparental disomy on chromosome 4. In conclusion, to the best of our knowledge, we describe the first patient with partial uniparental mero-isodisomy of chromosome 4 carrying a novel mutation in the wolframin gene. The clinical phenotype observed in the patient and the analysis performed suggest that the genetic variant detected is pathogenetic.<\/jats:p>","DOI":"10.3390\/ijms22158082","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T11:12:52Z","timestamp":1627470772000},"page":"8082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Genetic Variant in the WFS1 Gene in a Patient with Partial Uniparental Mero-Isodisomy of Chromosome 4"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-0012","authenticated-orcid":false,"given":"Maurizio","family":"Delvecchio","sequence":"first","affiliation":[{"name":"Metabolic Disease and Genetics Disorders Unit, Giovanni XXIII Children\u2019s Hospital, 70126 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Ortolani","sequence":"additional","affiliation":[{"name":"Metabolic Disease and Genetics Disorders Unit, Giovanni XXIII Children\u2019s Hospital, 70126 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-3482","authenticated-orcid":false,"given":"Orazio","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Aloi","sequence":"additional","affiliation":[{"name":"Clinica Pediatrica, LABSIEM, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Salina","sequence":"additional","affiliation":[{"name":"Clinica Pediatrica, LABSIEM, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco Claudio","family":"Susca","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-9902","authenticated-orcid":false,"given":"Pietro","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-6829","authenticated-orcid":false,"given":"Massimo","family":"Carella","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-5532","authenticated-orcid":false,"given":"Nicoletta","family":"Resta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology (DIMO), Division of Medical Genetics, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvira","family":"Piccinno","sequence":"additional","affiliation":[{"name":"Metabolic Disease and Genetics Disorders Unit, Giovanni XXIII Children\u2019s Hospital, 70126 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Ardinger, H.H., and Pagon, R.A. 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