A sibling case of Wolfram syndrome with a novel mutation Y652X in WFS1

We report on two Japanese siblings with Wolfram syndrome (WS) who were identified as carrying a novel mutation in Wolfram syndrome 1 (WFS1). The homozygous mutation, Y652X in exon 8, has not been reported in WS or low-frequency sensorineural hearing loss previously. The substitution is located at the beginning of the C-terminus of the protein, which is typically localized to the lumen of the endoplasmic reticulum (ER). This mutation predicts a truncated protein of 651 aa, with deletion of the entire C-terminal peptide, and was suggested to cause a severe phenotype. They developed a typical presentation, including symptoms such as deafness, diabetes insipidus, and visual disturbances at younger ages compared to those reported in the review. Moreover, they were also diagnosed with attention deficit hyperactivity disorder (ADHD), a neuropsychiatric disorder that manifests in early childhood as a deviation from normal development at the ages of 3 and 5 years. WS is known to be associated with neurological and psychiatric disorders, such as severe depression. However, co-occurrence of ADHD and WS has not been found in the literature; these cases were also interesting in this aspect.