A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily
A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily
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DOI：
10.1111/j.1365-2133.2005.06842.x
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发表时间：
2005-11-01
影响因子：
10.3
通讯作者：
Averna, MR
中科院分区：
文献类型：
--
作者：
Lupo, I;Cefalu, AB;Averna, MR
研究背景类脂质蛋白沉积症（Lipoid proteinosis，LP）是一种罕见的常染色体隐性遗传疾病，以声音嘶哑、皮肤疣状浸润和瘢痕形成为特征。细胞外基质蛋白1（ECM 1）基因内的突变导致LP。目的我们报告的ECM 1基因在西西里岛的LP患者的分子分析，以扩大这genodermatosis.Methods的突变谱，我们研究了一个32岁的女性出生的近亲父母谁被诊断为在11岁的LP。她具有对应于Urbach-Wiethe病的临床表型，其特征在于主要涉及皮肤和粘膜的丘疹/结节、硬化斑块和有时溃疡性病变，以及皮外特征如癫痫、声音嘶哑和神经精神异常。通过活检获得的临床受影响的皮肤样品在用苏木精和伊红、高碘酸-希夫（PAS）和PAS-双磷酸酶染色后进行分析。结果在ECM 1基因第6外显子发现一个纯合性无义突变C589 T（Q197 Ter）。外显子7是可变剪接的，外显子7中的移码突变导致ECM 1a转录物的消融，但不导致通常缺乏该外显子的较短ECM 1b转录物的消融。外显子6中的纯合无义或移码突变预计会影响全长ECM 1a和ECM 1b转录本，而ECM 1b应不受外显子7中类似类型突变的影响。有人认为，外显子7突变的个体比外显子6突变的个体具有稍微温和的表型。这是第一份报告，就一种新的突变的ECM 1基因负责隐性LP在西西里。
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.