The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1.
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.
Chan
Ien
I
Genetic Skin Disease Group, St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, The Guy's, King's College and St Thomas' School of Medicine, London, UK.
Liu
Lu
L
Hamada
Takahiro
T
Sethuraman
Gomathy
G
McGrath
John A
JA
D001323:Autoantibodies / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D012867:Skin / Q000473:pathology
D001323:Autoantibodies; C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins