R Squitti1, G Cerchiaro2, I Giovannoni3, P Francalanci3, M Siotto4, P Maffei5, C Ricordi6, M C Rongioletti7. 1. IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. 2. Center of Natural Sciences and Humanities, Federal University of ABC - UFABC, Santo André, São Paulo, Brazil. 3. Department of Pathology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 4. IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy. 5. Department of Medicine (DIMED), Clinica Medica 3, Padua University Hospital, Italy. 6. Diabetes Research Institute and Cell Transplant Center, University of Miami, Miami, FL, USA. 7. Department of Laboratory Medicine, Research and Development Division, 'San Giovanni Calibita', Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy.
Abstract
BACKGROUND: Wolfram Syndrome 1 (WS1) has been characterized on the basis of mutation in the WFS1 gene encoding a calcium storage wolframin endoplasmatic reticulum transmembrane glycoprotein. PATIENTS AND METHODS: We observed a WS 10-years old female subject, with Type 1 diabetes-mellitus (DM), that had compound heterozygous WSF1 mutations but without other symptoms generally observed in WS subjects, such as optic atrophy or neurodegeneration. RESULTS: Decreased copper, ceruloplasmin, and transferrin levels, pointing to a copper deficiency, were associated with a new c.18703A>G mutation in the ATP7B gene, while lower calcium levels were associated with WSF1 mutations. An omega-3 fatty acids therapy was administrated to the subject in the attempt to ameliorate diabetes symptoms, restored copper deficiency, and normal calcium levels. CONCLUSIONS: This specific case report provides new insights into the potential interplay of ATP7B mutation in shaping a milder WS clinical picture.
BACKGROUND: Wolfram Syndrome 1 (WS1) has been characterized on the basis of mutation in the WFS1 gene encoding a calcium storage wolframin endoplasmatic reticulum transmembrane glycoprotein. PATIENTS AND METHODS: We observed a WS 10-years old female subject, with Type 1 diabetes-mellitus (DM), that had compound heterozygous WSF1 mutations but without other symptoms generally observed in WS subjects, such as optic atrophy or neurodegeneration. RESULTS: Decreased copper, ceruloplasmin, and transferrin levels, pointing to a copper deficiency, were associated with a new c.18703A>G mutation in the ATP7B gene, while lower calcium levels were associated with WSF1 mutations. An omega-3 fatty acids therapy was administrated to the subject in the attempt to ameliorate diabetes symptoms, restored copper deficiency, and normal calcium levels. CONCLUSIONS: This specific case report provides new insights into the potential interplay of ATP7B mutation in shaping a milder WS clinical picture.
Authors: Malgorzata Zatyka; Gabriela Da Silva Xavier; Elisa A Bellomo; Wendy Leadbeater; Dewi Astuti; Joel Smith; Frank Michelangeli; Guy A Rutter; Timothy G Barrett Journal: Hum Mol Genet Date: 2014-09-30 Impact factor: 6.150