Wolfram syndrome (diabetes insipidus, diabetes, optic atrophy, and deafness): clinical and genetic study.
OBJECTIVE
Wolfram syndrome is an autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, diabetes (nonautoimmune), optic atrophy, and deafness (a set of conditions referred to as DIDMOAD). The WFS1 gene is located on the short arm of chromosome 4. Wolfram syndrome prevalence is 1 in 770,000 live births, with a 1 in 354 carrier frequency.


METHODS
We evaluated six Italian children from five unrelated families. Genetic analysis for Wolfram syndrome 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 exon 8.


CONCLUSIONS
Phenotype-genotype correlation is difficult, and the same mutation gives very different phenotypes. Severely inactivating mutations result in a more severe phenotype than mildly inactivating ones. Clinical follow-up showed the progressive syndrome's seriousness.
d'Annunzio
Giuseppe
G
Pediatric Clinic, University of Genoa, G. Gaslini Institute, Genoa, Italy. giuseppedannunzio@ospedale-gaslini.ge.it
Minuto
Nicola
N
D'Amato
Elena
E
de Toni
Teresa
T
Lombardo
Fortunato
F
Pasquali
Lorenzo
L
Lorini
Renata
R
D001921:Brain / Q000473:pathology; D002648:Child; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014929:Wolfram Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
D008565:Membrane Proteins; C114987:wolframin protein