{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:03:43Z","timestamp":1788455023859,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background:\u00a0WFS1-spectrum disorders are caused by a mutation in the WFS1 gene. The term includes a wide range of rare disorders, from the most severe Wolfram syndrome with autosomal recessive inheritance to milder clinical manifestations with a single causative variant in the WFS1 gene, such as Wolfram-like syndrome, low-frequency sensorineural hearing loss (LFSNHL), isolated diabetes mellitus (DM), nonsyndromic optic atrophy (OA), and isolated congenital cataracts. Methods: The aim of this study was to evaluate genotype\u2013phenotype correlations in Polish patients with WFS1-spectrum disorders. The study group constituted 22 patients (10 F; 12 M), including 10 patients (3 F; 7 M) referred to the Outpatient Clinic for Rare Diseases in Children and Adolescents and Diabetogenetics between 2019 and 2024 with clinical symptoms suggestive of WFS1-spectrum disorders, and 12 of their first-degree relatives (7 F; 5 M) from 10 families in Poland. Molecular testing was performed using tNGS (Targeted Next Generation Sequencing; Illumina) and analyzed for variants in the WFS1 gene. Results: Thirteen different variants in the WFS1 gene were found in 22 individuals (10 patients and family members), including the identification of two new variants (c.1535T&gt;C and c.2485C&gt;G). All patients had hyperglycemia or DM, hearing impairment, OA, or a combination of these symptoms. Four patients in the study group were diagnosed with Wolfram syndrome and all were compound heterozygotes for variants in the WFS1 gene. Conclusions: The evaluation of molecular characteristics in combination with clinical symptoms broadens the understanding of WFS1-spectrum disorders and allows more accurate management and prognosis for patients with this diagnosis.<\/jats:p>","DOI":"10.3390\/genes15121592","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T09:38:15Z","timestamp":1733996295000},"page":"1592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Patients with a Wide Range of Disorders Related to WFS1 Gene Variants: Novel Mutations and Genotype\u2013Phenotype Correlations"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8779-3907","authenticated-orcid":false,"given":"Julia","family":"Grzybowska-Adamowicz","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Gadzalska","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Jakiel","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Ju\u015bci\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Gorz\u0105dek","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2760-2397","authenticated-orcid":false,"given":"Sebastian","family":"Skoczylas","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"P\u0142oszaj","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142awa","family":"Jarosz-Chobot","sequence":"additional","affiliation":[{"name":"Department of Children\u2019s Diabetolog and Lifestyle Medicine, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-1959","authenticated-orcid":false,"given":"Irina","family":"Kowalska","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"My\u015bliwiec","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Diabetology and Endocrinology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Szadkowska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8781-4469","authenticated-orcid":false,"given":"Agnieszka","family":"Zmys\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rigoli, L., Caruso, V., Salzano, G., and Lombardo, F. 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