Pathogenetic mechanism of lipoid proteinosis caused by mutation of the extracellular matrix protein 1 gene

Abstract

Lipoid proteinosis (LP) is a rare form of dermatosis with autosomal recessive inheritance. The present study hypothesized that an extracellular matrix protein 1 (ECM1) gene mutation forms the pathological basis of LP. The association between ECM1 mutation and LP; however, requires further investigation and was thus investigated in the present study. Injury skin tissue samples from patients with LP were collected, along with venous blood samples for genomic DNA extraction. Immunohistochemical staining was performed. Polymerase chain reaction (PCR) was then used to obtain an ECM1 gene fragment, which was sequenced and compared with healthy individuals. Histopathological examination revealed that all included patients fitted the features of LP and PCR amplification of the ECM1 gene in all patients obtained positive results. Patients with LP in the present study exhibited point mutations in the ECM1 gene, including one homozygous mutation (C220G) as previously reported, and one novel homozygous mutation c.508insCTG and two heterozygous mutations (C220G/P.R481X and c507delT/c.l473delT). LP is correlated with ECM1 gene mutation.

Extracellular Matrix Protein 1 Regulates Colorectal Cancer Cell Proliferative, Migratory, Invasive and Epithelial-Mesenchymal Transition Activities Through the PI3K/AKT/GSK3β/Snail Signaling Axis

“…The secretory glycoprotein, extracellular matrix protein 1 (ECM1), is associated with physiological processes including angiogenesis, the proliferation of epithelial cells, and skin differentiation, in addition to playing a role in tumor progression ( 3 , 4 ). Recent studies have detected ECM1 overexpression in bladder cancer ( 5 ), glioblastoma ( 6 ), thyroid cancer ( 7 ), cholangiocarcinoma ( 8 ), and other epithelial malignancies ( 9 ), and the overexpression of ECM1 has also been shown to be related to the poor prognosis of cancer patients, such as pancreatic cancer ( 10 ), breast cancer ( 11 ), gastric cancer ( 12 ) and hepatocellular cancer patients ( 13 ).…”

Lipoid Proteinosis - A Rarity in An Adult

“…[12] Mutations can be heterozygous and homozygous type. [13] The unstable extracellular matrix might cause neighbouring cells to overproduce proteins and other materials resulting in excess substance production which accumulates in tissues and deposits, the hallmark feature of LP. [14] It is characterized by generalized thickening, scarring, infiltration of mucosae and deposition of hyaline like material in skin, oral cavity, larynx and internal organs.…”

“…[1] The prognosis of LP is good and patients with this disorder usually have normal life expectancy even after upper respiratory tract is involved and breathing is compromised. [13]…”

Lipoid Proteinosis

“…Genotype-phenotype correlations are not consistent across different families because the ECM1 gene has several transcripts, and each may be differently active in different tissues including the vocal cords and the brain. 2,3 Lipoid proteinosis usually presents with features related to involvement of the skin and mucous membrane of the respiratory tract. Ocular and neurological disease may also occur.…”

“…Loss of protein-protein interactions due to ECM1 mutation results in deposition of hyaline material in the skin, mucous membrane, and other organs. Genotype-phenotype correlations are not consistent across different families because the ECM1 gene has several transcripts, and each may be differently active in different tissues including the vocal cords and the brain …”