Patients with a Wide Range of Disorders Related to Gene Variants: Novel Mutations and Genotype-Phenotype Correlations.

-spectrum disorders are caused by a mutation in the 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 gene, such as Wolfram-like syndrome, low-frequency sensorineural hearing loss (LFSNHL), isolated diabetes mellitus (DM), nonsyndromic optic atrophy (OA), and isolated congenital cataracts. The aim of this study was to evaluate genotype-phenotype correlations in Polish patients with -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 -spectrum disorders, and 12 of their first-degree relatives (7 F; 5 M) from 10 families in Poland. Molecular testing was performed using tNGS (; Illumina) and analyzed for variants in the gene. : Thirteen different variants in the gene were found in 22 individuals (10 patients and family members), including the identification of two new variants (c.1535T>C and c.2485C>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 gene. The evaluation of molecular characteristics in combination with clinical symptoms broadens the understanding of -spectrum disorders and allows more accurate management and prognosis for patients with this diagnosis.