TY - JOUR
T1 - Wolfram syndrome 1 in the Italian population. genotype–phenotype correlations
AU - Rigoli, Luciana
AU - Aloi, Concetta
AU - Salina, Alessandro
AU - Di Bella, Chiara
AU - Salzano, Giuseppina
AU - Caruso, Rosario
AU - Mazzon, Emanuela
AU - Maghnie, Mohamad
AU - Patti, Giuseppa
AU - D’Annunzio, Giuseppe
AU - Lombardo, Fortunato
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85069899418&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069899418&partnerID=8YFLogxK
U2 - 10.1038/s41390-019-0487-4
DO - 10.1038/s41390-019-0487-4
M3 - Article
C2 - 31266054
AN - SCOPUS:85069899418
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
ER -