TY - JOUR
T1 - A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily
AU - Daniele, Ornella
AU - Cefalu', Angelo Baldassare
AU - Bongiorno, Maria Rita
AU - Savettieri, Giovanni
AU - Camarda, Rosolino
AU - Averna, Maurizio
AU - Valenti, Vincenza
AU - Valenti, Vincenza
AU - Cefalu, Angelo B.
AU - Noto, Davide
AU - Averna, Maurizio R.
AU - Lupo, Innocenzo
AU - Arico', Mario
PY - 2005
Y1 - 2005
N2 - 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.OBJECTIVES: 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.
AB - 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.OBJECTIVES: 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.
UR - http://hdl.handle.net/10447/7074
M3 - Article
VL - 153
SP - 1019
EP - 1022
JO - British Journal of Dermatology
JF - British Journal of Dermatology
SN - 0007-0963
ER -