Study On Mutations Of ECM1 In Lipoid Proteinosis

BackgroundLipoid proteinosis (LP) also called Urbach-Weithe disease or lipoidosis cutis et mucosae, which was first described by Urbach and Weithe in 1929. The disorder is an autosomal recessive genodermatosis. LP is a rare condition with a characteristic of cutaneous lesions occurring, involving mucosal membranes of upper respiratory tract, upper digestive tract, central nervous system, lymph nodes and striated muscles. It is characterized deposition of abnormal lipid and protein. The usual presentation is with hoarseness of voice and pox-like skin scars in early childhood. Adopting genome-wide linkage analysis, positional candidate gene approach and Sequencing, Hamada identified the genetic defect to be a loss-of-function mutation or reduced expression of the gene encoding extracellular matrix protein 1 (ECM1) on chromosome Iq21 in 2002. It is a glycoprotein which plays a role as a secreted protein in the dermis, and having a function in binding with other proteins to regulate their activity. ECMl affects on epidermal differentiation, binding to dermal collagen and proteoglycan and regulating angiogenesis. It expresses on the basement membrane fibrous proteins and growth factor by binding to proteoglycan, also play a important role on skin homeostasis. ECM1 has 10 exons, most mutations are in exon 6 and exon 7. To the best of our knowledge,51 mutations were found on ECMl gene.ObjectiveTo identify the pathogensis mutations of ECM1 in 5 patients with LP.MethodsGenomic DNA was isoloated from the blood samlies of 5 patients with LP and their family members. According to the information of all the exons of ECM1 supplied by UCSC Genome, we design a pair of primers for each exon and amplify the DNA template. The amplified DNA were directly sequenced and analyzed.ResultsWe got the predicted segments when using the 10 pairs of primers to amplify the sample. By directly sequencing the amplified DNA and analyzing the sequencing results with UCSC BLAT, We identifed a recrrent mutation as well as identified 3 novel mutations in the ECM1 gene, which are c.508insCTG, p.C220G/p.R481X and c.507delT/c.1473delT.ConclusionWe find a existing mutation and identified 3 novel mutations, which are due to common polymorphism.