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

We studied 45 patients with Wolfram syndrome 1 (WS1) to describe their clinical history and to search for possible genotype-phenotype correlations.

Clinical criteria contributing to WS1 diagnosis were analyzed. The patients were classified into three genotypic classes according to type of detected mutations.

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.

Our study suggested that molecular WFS1 typing is a useful tool for early assessment of clinical history, follow-up, and prognosis of WS1.