WOLFRAM SYNDROME (DIABETES INSIPIDUS, DIABETES MELLITUS, OPTIC ATROPHY AND DEAFNESS [DIDMOAD]: SIMILAR PHENOTYPES BY DIFFERENT GENETIC MECHANISMS
- Giuseppe d'Annunzio, MD (giuseppedannunzio{at}ospedale-gaslini.ge.it)*,
- Nicola Minuto, MD*,
- Elena D'Amato, PhD*,
- Teresa de Toni, MD*,
- Fortunato Lombardo†,
- Lorenzo Pasquali, MD* and
- Renata Lorini, MD*
- *Pediatric Clinic, University of Genoa, G. Gaslini Institute, Genoa, Italy
- †Department of Pediatric Sciences, University of Messina, Messina, Italy
Abstract
Objective: Wolfram Syndrome (WS) is an autosomal recessive neurodegenerative disorder characterized by non autoimmune diabetes mellitus, optic atrophy, diabetes insipidus and deafness or “DIDMOAD” (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). WFS1 gene is located on the short arm of chromosome 4. WS prevalence is 1/770.000 live births, with 1/354 carrier frequency.
Research Design and Methods: We evaluated 6 Italian children from 5 unrelated families. Genetic analysis for WS was performed by PCR amplification and direct sequencing.
Results: Mutation screening revealed five distinct variants: one novel mutation (c.1346C>T; p.T449I) and four previously described, all located in the exon 8.
Conclusions: Phenotype/genotype correlation is difficult and the same mutation gives very different phenotypes. Severely inactivating mutations result in a more sever phenotype than mildly inactivating ones. Clinical follow-up showed the progressive syndrome seriousness.
Footnotes
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- Received February 13, 2008.
- Accepted June 7, 2008.
- Copyright © American Diabetes Association
