The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Takahiro Hamada - One of the best experts on this subject based on the ideXlab platform.
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the molecular basis of lipoid Proteinosis mutations in extracellular matrix protein 1
Experimental Dermatology, 2007Co-Authors: I. Chan, Lu Liu, Takahiro Hamada, Gomathy Sethuraman, John A McgrathAbstract:Lipoid Proteinosis (OMIM 247100), also known as Urbach-Wiethe disease or hyalinosis cutis et mucosae, is a rare autosomal recessive disorder characterized by generalized thickening and scarring of the skin and mucosae. In 2002, the disorder was mapped to a locus on chromosome 1q21 and pathogenic mutations were identified in the ECM1 gene, which encodes for the glycoprotein extracellular matrix protein 1 (ECM1). ECM1 has since been shown to have several important biological functions. It has a role in the structural organization of the dermis (binding to perlecan, matrix metalloproteinase-9 and fibulin) as well as being targeted as an autoantigen in the acquired disease lichen sclerosus. ECM1 also shows over-expression in certain malignancies and is abnormally expressed in chronologically aged and photo-aged skin. Thus far, 26 different inherited mutations in ECM1 have been reported in lipoid Proteinosis. In this article, we provide an update on the molecular pathology of lipoid Proteinosis, including the addition of 15 new mutations in ECM1 to the mutation database, and review the biological functions of the ECM1 protein in health and disease.
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Clinical and molecular abnormalities in lipoid Proteinosis.
European journal of dermatology : EJD, 2005Co-Authors: S Desmet, Takahiro Hamada, John A Mcgrath, Stijn Devos, Ien Chan, Ingeborg Dhooge, Jean NaeyaertAbstract:Lipoid Proteinosis (hyalinosis cutis et mucosae) is a rare, autosomal recessive disease. The main clinicopathological features comprise skin and mucous membrane infiltration and scarring with deposition of hyaline material. In this report, we describe a 6-year-old boy in whom a diagnosis of lipoid Proteinosis was first suspected when he presented with blisters and erosions at 4 years, a history of life-long dysphonia and a previous epileptic convulsion. The diagnosis was confirmed by histology and identification of a homozygous frameshift mutation, 501insC, in exon 6 of the gene encoding extracellular matrix protein 1, ECM1. Lipoid Proteinosis may show protean clinical features and be difficult to diagnose on clinical grounds alone. This case report illustrates that lipoid Proteinosis may show protean clinical features and yet remain undiagnosed for many years. Although the gold standard for definite diagnosis remains histology, molecular characterisation of the gene mutation will add to our understanding of genotype-phenotype correlation and perhaps to the development of a rationale for future therapeutics.
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extracellular matrix protein 1 gene ecm1 mutations in lipoid Proteinosis and genotype phenotype correlation
Journal of Investigative Dermatology, 2003Co-Authors: I. Chan, Takahiro Hamada, Noritaka Oyama, Andrew P South, Vesarat Wessagowit, G H S Ashton, Apatorn Siriwattana, Prachiya Jewhasuchin, S CharuwichitratanaAbstract:The autosomal recessive disorder lipoid Proteinosis results from mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in several tissues (including skin) and composed of two alternatively spliced isoforms, ECM1a and ECM1b, the latter lacking exon 7 of this 10-exon gene (ECM1). To date, mutations that either affect ECM1a alone or perturb both ECM1 transcripts have been demonstrated in six cases. However, lipoid Proteinosis is clinically heterogeneous with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurological abnormalities such as temporal lobe epilepsy. In this study, we sequenced ECM1 in 10 further unrelated patients with lipoid Proteinosis to extend genotype-phenotype correlation and to add to the mutation database. We identified seven new homozygous nonsense or frameshift mutations: R53X (exon 3); 243delG (exon 4); 507delT (exon 6); 735delTG (exon 7); 785delA (exon 7); 892delC (exon 7) and 1190insC (exon 8), as well as two new compound heterozygous mutations: W160X/F167I (exon 6) and 542insAA/R243X (exons 6/7), none of which were found in controls. The mutation 507delT occurred in two unrelated subjects on different ECM1 haplotypes and may therefore represent a recurrent mutation in lipoid Proteinosis. Taken with the previously documented mutations in ECM1, this study supports the view that exons 6 and 7 are the most common sites for ECM1 mutations in lipoid Proteinosis. Clinically, it appears that mutations outside exon 7 are usually associated with a slightly more severe mucocutaneous lipoid Proteinosis phenotype, but neurological features do not show any specific genotype-phenotype correlation.
John A Mcgrath - One of the best experts on this subject based on the ideXlab platform.
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Chapter 23 - Lipoid Proteinosis
Handbook of clinical neurology, 2015Co-Authors: John A McgrathAbstract:Lipoid Proteinosis is a rare autosomal recessive disorder caused by mutations in ECM1, encoding extracellular matrix protein 1, a glycoprotein expressed in many organs and which has important protein–protein interactions in tissue homeostasis. Although the disease usually presents clinically with warty infiltration of the skin and mucous membranes and a hoarse voice, neuropsychological and neuropsychiatric abnormalities are often prominent features. There may be bean- or comma-shaped intracranial calcifications, often selectively affecting the amygdala. Patients with lipoid Proteinosis therefore have been used as models for demonstrating physiologic and pathologic abnormalities of the amygdala with respect to fear processing, affect and cognition, anxiety and memory. Clinically, patients may also have epilepsy, especially involving the temporal lobes. Less common or rare disease associations are headache (including migraine), ataxia, dizziness, schizophrenia, generalized dystonia, transient brachiofacial paralysis, and intracerebral hemorrhage. Beyond the foci of calcification, the cause of the neurologic abnormalities in lipoid Proteinosis is unknown, although the ECM1 protein can normally bind to various extracellular matrix proteins and glycosaminoglycans as well as certain enzymes, including matrix metalloproteinase 9. Loss of key protein–protein interactions may underscore some of the disease pathophysiology. There is currently no effective treatment for lipoid Proteinosis and clinical care is largely supportive.
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the molecular basis of lipoid Proteinosis mutations in extracellular matrix protein 1
Experimental Dermatology, 2007Co-Authors: I. Chan, Lu Liu, Takahiro Hamada, Gomathy Sethuraman, John A McgrathAbstract:Lipoid Proteinosis (OMIM 247100), also known as Urbach-Wiethe disease or hyalinosis cutis et mucosae, is a rare autosomal recessive disorder characterized by generalized thickening and scarring of the skin and mucosae. In 2002, the disorder was mapped to a locus on chromosome 1q21 and pathogenic mutations were identified in the ECM1 gene, which encodes for the glycoprotein extracellular matrix protein 1 (ECM1). ECM1 has since been shown to have several important biological functions. It has a role in the structural organization of the dermis (binding to perlecan, matrix metalloproteinase-9 and fibulin) as well as being targeted as an autoantigen in the acquired disease lichen sclerosus. ECM1 also shows over-expression in certain malignancies and is abnormally expressed in chronologically aged and photo-aged skin. Thus far, 26 different inherited mutations in ECM1 have been reported in lipoid Proteinosis. In this article, we provide an update on the molecular pathology of lipoid Proteinosis, including the addition of 15 new mutations in ECM1 to the mutation database, and review the biological functions of the ECM1 protein in health and disease.
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Clinical and molecular abnormalities in lipoid Proteinosis.
European journal of dermatology : EJD, 2005Co-Authors: S Desmet, Takahiro Hamada, John A Mcgrath, Stijn Devos, Ien Chan, Ingeborg Dhooge, Jean NaeyaertAbstract:Lipoid Proteinosis (hyalinosis cutis et mucosae) is a rare, autosomal recessive disease. The main clinicopathological features comprise skin and mucous membrane infiltration and scarring with deposition of hyaline material. In this report, we describe a 6-year-old boy in whom a diagnosis of lipoid Proteinosis was first suspected when he presented with blisters and erosions at 4 years, a history of life-long dysphonia and a previous epileptic convulsion. The diagnosis was confirmed by histology and identification of a homozygous frameshift mutation, 501insC, in exon 6 of the gene encoding extracellular matrix protein 1, ECM1. Lipoid Proteinosis may show protean clinical features and be difficult to diagnose on clinical grounds alone. This case report illustrates that lipoid Proteinosis may show protean clinical features and yet remain undiagnosed for many years. Although the gold standard for definite diagnosis remains histology, molecular characterisation of the gene mutation will add to our understanding of genotype-phenotype correlation and perhaps to the development of a rationale for future therapeutics.
I. Chan - One of the best experts on this subject based on the ideXlab platform.
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the molecular basis of lipoid Proteinosis mutations in extracellular matrix protein 1
Experimental Dermatology, 2007Co-Authors: I. Chan, Lu Liu, Takahiro Hamada, Gomathy Sethuraman, John A McgrathAbstract:Lipoid Proteinosis (OMIM 247100), also known as Urbach-Wiethe disease or hyalinosis cutis et mucosae, is a rare autosomal recessive disorder characterized by generalized thickening and scarring of the skin and mucosae. In 2002, the disorder was mapped to a locus on chromosome 1q21 and pathogenic mutations were identified in the ECM1 gene, which encodes for the glycoprotein extracellular matrix protein 1 (ECM1). ECM1 has since been shown to have several important biological functions. It has a role in the structural organization of the dermis (binding to perlecan, matrix metalloproteinase-9 and fibulin) as well as being targeted as an autoantigen in the acquired disease lichen sclerosus. ECM1 also shows over-expression in certain malignancies and is abnormally expressed in chronologically aged and photo-aged skin. Thus far, 26 different inherited mutations in ECM1 have been reported in lipoid Proteinosis. In this article, we provide an update on the molecular pathology of lipoid Proteinosis, including the addition of 15 new mutations in ECM1 to the mutation database, and review the biological functions of the ECM1 protein in health and disease.
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extracellular matrix protein 1 gene ecm1 mutations in lipoid Proteinosis and genotype phenotype correlation
Journal of Investigative Dermatology, 2003Co-Authors: I. Chan, Takahiro Hamada, Noritaka Oyama, Andrew P South, Vesarat Wessagowit, G H S Ashton, Apatorn Siriwattana, Prachiya Jewhasuchin, S CharuwichitratanaAbstract:The autosomal recessive disorder lipoid Proteinosis results from mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in several tissues (including skin) and composed of two alternatively spliced isoforms, ECM1a and ECM1b, the latter lacking exon 7 of this 10-exon gene (ECM1). To date, mutations that either affect ECM1a alone or perturb both ECM1 transcripts have been demonstrated in six cases. However, lipoid Proteinosis is clinically heterogeneous with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurological abnormalities such as temporal lobe epilepsy. In this study, we sequenced ECM1 in 10 further unrelated patients with lipoid Proteinosis to extend genotype-phenotype correlation and to add to the mutation database. We identified seven new homozygous nonsense or frameshift mutations: R53X (exon 3); 243delG (exon 4); 507delT (exon 6); 735delTG (exon 7); 785delA (exon 7); 892delC (exon 7) and 1190insC (exon 8), as well as two new compound heterozygous mutations: W160X/F167I (exon 6) and 542insAA/R243X (exons 6/7), none of which were found in controls. The mutation 507delT occurred in two unrelated subjects on different ECM1 haplotypes and may therefore represent a recurrent mutation in lipoid Proteinosis. Taken with the previously documented mutations in ECM1, this study supports the view that exons 6 and 7 are the most common sites for ECM1 mutations in lipoid Proteinosis. Clinically, it appears that mutations outside exon 7 are usually associated with a slightly more severe mucocutaneous lipoid Proteinosis phenotype, but neurological features do not show any specific genotype-phenotype correlation.
C Medrano - One of the best experts on this subject based on the ideXlab platform.
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Pulmonary alveolar Proteinosis: prolonged spontaneous remission in two patients
The European respiratory journal, 1991Co-Authors: Ma Martinez-lopez, G Gomez-cerezo, C Villasante, F Molina, S Diaz, J Cobo, C MedranoAbstract:Pulmonary alveolar Proteinosis is a rare idiopathic diffuse airspace disease characterized by intra-alveolar accumulation of large quantities of lipoproteinaceous material, with preservation of the lung interstitium. The clinical course of pulmonary alveolar Proteinosis is variable. Spontaneous resolution is known to occur in up to a quarter of the cases. We describe two patients with untreated pulmonary alveolar Proteinosis who experienced complete clinical, functional and radiographic resolution. In follow-up periods of fourteen and six years, both patients have remained asymptomatic.
Bruce C. Trapnell - One of the best experts on this subject based on the ideXlab platform.
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Therapy options in pulmonary alveolar Proteinosis
Therapeutic advances in respiratory disease, 2010Co-Authors: Maurizio Luisetti, Zamir Kadija, Francesca Mariani, Giuseppe Rodi, Ilaria Campo, Bruce C. TrapnellAbstract:Pulmonary alveolar Proteinosis is a rare condition characterized by the accumulation of lipoproteinaceous material within the airspaces, resulting in impaired gas transfer, and clinical manifestations ranging from asymptomatic to severe respiratory failure. To the best of the authors’ knowledge, there are only a few conditions whose natural history has been so dramatically changed by the influence of advances in basic science, clinical medicine, and translational research in therapeutic approaches. Whole-lung lavage is the current standard of care and it plays a critical role as a modifier factor of the natural history of Proteinosis. That notwithstanding, the identification of autoantibodies neutralizing granulocyte-macrophage colony-stimulating factor in serum and lung of patients affected by the form of Proteinosis previously referred to as idiopathic, has opened the way to novel therapeutic options, such as supplementation of exogenous granulocyte-macrophage colony-stimulating factor, or strategies ai...
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Pulmonary Alveolar Proteinosis
The New England journal of medicine, 2003Co-Authors: Bruce C. Trapnell, Jeffrey A. Whitsett, Koh NakataAbstract:In acquired pulmonary alveolar Proteinosis, lipids and proteins accumulate within the alveoli because alveolar macrophages cannot catabolize surfactants. Surprisingly, alveolar macrophages require granulocyte–macrophage colony-stimulating factor (GM-CSF) to perform this function. Autoantibodies against GM-CSF may cause pulmonary alveolar Proteinosis.
