Wolfram syndrome 1 in the Italian population: genotype–phenotype correlations

Objectives We studied 45 patients with Wolfram syndrome 1 (WS1) to describe their clinical history and to search for possible genotype–phenotype correlations. Methods Clinical criteria contributing to WS1 diagnosis were analyzed. The patients were classified into three genotypic classes according to type of detected mutations. Results WS1 prevalence in Italy is 0.74/1,000,000. All four manifestations of DIDMOAD were found in 46.7% of patients. Differently combined WS1 clinical features were detected in 53.3% of patients. We found 35 WFS1 different mutations and a novel missense mutation, c.1523A>G. WS1 patients were homozygotes or compound heterozygotes for WFS1 mutations except for 2 heterozygote patients (4.5%). Each genotypic group exhibited a different age onset of DM, D, and DI but not of OA. Genotypic Group 2 patients manifested a lower number of clinical manifestations compared to Groups 1 and 3. Moreover, genotypic Group 1 patients tended to have a shorter survival time than the other groups. No differences were found regarding type of clinical pictures. Conclusions Our study suggested that molecular WFS1 typing is a useful tool for early assessment of clinical history, follow-up, and prognosis of WS1.