title: Clinical picture, evolution and peculiar molecular findings in a very large pedigree with Wolfram syndrome.
abstract: 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.
authors.affiliation: Department of Pediatric Sciences, University Hospital, Messina, Italy.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Lombardo
authors.forename: Pietro
authors.initials: P
authors.lastname: Chiurazzi
authors.forename: Konstanze
authors.initials: K
authors.lastname: Hörtnagel
authors.forename: Teresa
authors.initials: T
authors.lastname: Arrigo
authors.forename: Mariella
authors.initials: M
authors.lastname: Valenzise
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Messina
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Salzano
authors.forename: Ignazio
authors.initials: I
authors.lastname: Barberi
authors.forename: Filippo
authors.initials: F
authors.lastname: De Luca
mesh_terms: 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*
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; C114987:wolframin protein