A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2

作者：Mozzillo Enza^*; Delvecchio Maurizio; Carella Massimo; Grandone Elvira; Palumbo Pietro; Salina Alessandro; Aloi Concetta; Buono Pietro; Izzo Antonella; D' Annunzio Giuseppe; Vecchione Gennaro; Orrico Ada; Genesio Rita; Simonelli Francesca; Franzese Adriana

来源：BMC Medical Genetics, 2014, 15(1): 88.

DOI：10.1186/1471-2350-15-88

• CISD2
• Optic neuropathy
• Non-autoimmune diabetes mellitus
• Novel mutation
• Platelet aggregation
• Sensorineural hearing loss
• SNP-array
• Upper intestinal ulcers
• Wolfram syndrome

Background: Wolfram Syndrome type 2 (WFS2) is considered a phenotypic and genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and psychiatric disorders, and for the presence of bleeding upper intestinal ulcers and defective platelet aggregation. After the first report of consanguineous Jordanian patients, no further cases of WFS2 have been reported worldwide. We describe the first Caucasian patient affected by WFS2. %26lt;br%26gt;Case presentation: The proband was a 17 year-old girl. She presented diabetes mellitus, optic neuropathy, intestinal ulcers, sensorineural hearing loss, and defective platelet aggregation to ADP. Genetic testing showed a novel homozygous intragenic deletion of CISD2 in the proband. Her brother and parents carried the heterozygous mutation and were apparently healthy, although they showed subclinical defective platelet aggregation. Long runs of homozygosity analysis from SNP-array data did not show any degree of parental relationship, but the microsatellite analysis confirmed the hypothesis of a common ancestor. %26lt;br%26gt;Conclusion: Our patient does not show optic atrophy, one of the main diagnostic criteria for WFS, but optic neuropathy. Since the %26quot;asymptomatic%26quot; optic atrophy described in Jordanian patients is not completely supported, we could suppose that the ocular pathology in Jordanian patients was probably optic neuropathy and not optic atrophy. Therefore, as optic atrophy is required as main diagnostic criteria of WFS, it might be that the so-called WFS2 could not be a subtype of WFS. In addition, we found an impaired aggregation to ADP and not to collagen as previously reported, thus it is possible that different experimental conditions or inter-patient variability can explain different results in platelet aggregation. Further clinical reports are necessary to better define the clinical spectrum of this syndrome and to re-evaluate its classification.

• 出版日期2014-7-24