title: A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily.
abstract: BACKGROUND
  Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LP.
  
  
  OBJECTIVE
  We report the molecular analysis of the ECM1 gene in a Sicilian patient with LP in order to extend the mutation spectrum of this genodermatosis.
  
  
  METHODS
  We studied a 32-year-old female born from consanguineous parents who was diagnosed at the age of 11 years as having LP. She has a clinical phenotype corresponding to Urbach-Wiethe disease characterized by papules/nodules, indurated plaques and sometimes ulcerated lesions primarily involving the skin and mucous membranes, and extracutaneous features such as epilepsy, hoarseness of the voice and neuropsychiatric abnormalities. Samples of clinically affected skin obtained by biopsies were analysed after staining with haematoxylin and eosin, periodic acid-Schiff (PAS), and PAS-diastase. The whole ECM1 gene was analysed by direct sequencing.
  
  
  RESULTS
  We identified a homozygous nonsense mutation in exon 6 of the ECM1 gene, C589T (Q197Ter).
  
  
  CONCLUSIONS
  Over 60% of mutations occur in exons 6 and 7. Exon 7 is alternatively spliced and frameshift mutations in exon 7 lead to ablation of the ECM1a transcript, but not the shorter ECM1b transcript that normally lacks this exon. Homozygous nonsense or frameshift mutations in exon 6 are predicted to affect both full-length ECM1a and ECM1b transcripts, whereas ECM1b should be unaffected for similar types of mutation in exon 7. It has been suggested that individuals with mutations in exon 7 have a slightly milder phenotype than those with exon 6 mutations. This is the first report with respect to a novel mutation of the ECM1 gene responsible for recessive LP in Sicily.
authors.affiliation: Department of Dermatology, Institute of Neurology, University of Palermo, Palermo, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Lupo
authors.forename: A B
authors.initials: AB
authors.lastname: Cefalu
authors.forename: M R
authors.initials: MR
authors.lastname: Bongiorno
authors.forename: O
authors.initials: O
authors.lastname: Daniele
authors.forename: V
authors.initials: V
authors.lastname: Valenti
authors.forename: D
authors.initials: D
authors.lastname: Noto
authors.forename: R
authors.initials: R
authors.lastname: Camarda
authors.forename: G
authors.initials: G
authors.lastname: Savettieri
authors.forename: M
authors.initials: M
authors.lastname: Aricò
authors.forename: M R
authors.initials: MR
authors.lastname: Averna
mesh_terms: D000328:Adult; D001483:Base Sequence; D001706:Biopsy; D018389:Codon, Nonsense; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D012802:Sicily; D012873:Skin Diseases, Genetic / Q000235:genetics* / Q000473:pathology
chemical_list: D018389:Codon, Nonsense; C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins