Clinical picture, evolution and peculiar molecular findings in a very large pedigree with Wolfram syndrome.
OBJECTIVE
a) To describe a very extended inbred pedigree with Wolfram syndrome (WS) (OMIM #222300); b) to report both the clinical picture and evolution in this large family and a peculiar mutation which has been reported hitherto only in Italian patients.


METHODS
The five-generation pedigree from Sicily was reconstructed through a proband with all the main manifestation of WS, born to a couple of healthy consanguineous parents. DNA examination was performed in both patients and healthy family members.


RESULTS
In all seven patients we found a homozygous 16-bp deletion in exon 8 of the WFS1 gene that introduces a stop codon in position 454.


CONCLUSIONS
This inbred pedigree is the largest with WS described in the literature. Its analysis definitively confirms the view of autosomal recessive inheritance in WS. The 16-bp deletion appears to be a relatively frequent mutation only in Italian patients. Before examining the entire coding region of the WSF1 gene a preliminary screening for the 16-bp deletion in exon 8 might be suggested when a new Italian case of WS is investigated.
Lombardo
Fortunato
F
Department of Pediatric Sciences, University Hospital, Messina, Italy.
Chiurazzi
Pietro
P
Hörtnagel
Konstanze
K
Arrigo
Teresa
T
Valenzise
Mariella
M
Meitinger
Thomas
T
Messina
Maria Francesca
MF
Salzano
Giuseppina
G
Barberi
Ignazio
I
De Luca
Filippo
F
D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D018076:DNA, Complementary; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010375:Pedigree; D014929:Wolfram Syndrome / Q000235:genetics* / Q000473:pathology*
D018076:DNA, Complementary; D008565:Membrane Proteins; C114987:wolframin protein