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Updated: Aug 11, 2026

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Published on: August 8, 2022
Clinical picture, evolution and peculiar molecular findings in a very large pedigree with Wolfram syndrome
Fortunato Lombardo1, Pietro Chiurazzi, Konstanze Hörtnagel
1Department of Pediatric Sciences, University Hospital, Messina, Italy.
Objectives:
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.
Design:
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.
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