A Specific Defect in Glycosylation of Epidermal Cell Membranes

Fine, Jo‐David

doi:10.1001/archderm.1985.01660100072018

Cited by 13 publications

(1 citation statement)

References 30 publications

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“…This decrease in glucosyltransferase activity was limited to this enzyme, and lysyl hydroxylase and hydroxylysyl galactosyltransferase activities, as determined in skin biopsy specimens, were normal [23]. How the deficiency in galactosylhydroxylysineglucosyltransferase, an enzyme primarily involved in post-translational modification of collagens might cause EB simplex is unclear, but it could serve as a modifier of the severity of EB phenotype [15] as a specific defect in glycosylation of epidermal cell membranes has been reported in EB simplex [24]. Previously, skin blistering has also been reported in patients with extensive pulmonary and renal involvement due to mutations in the ITGA3 gene encoding 3 subunit of the 31 integrin complex [25].…”

Section: Discussionmentioning

confidence: 94%

Mutations in PLOD3, encoding lysyl hydroxylase 3, cause a complex connective tissue disorder including recessive dystrophic epidermolysis bullosa-like blistering phenotype with abnormal anchoring fibrils and type VII collagen deficiency

Vahidnezhad

Youssefian²,

Saeidian

et al. 2019

Matrix Biology

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Epidermolysis bullosa (EB), the paradigm of heritable skin fragility disorders, is associated with mutations in as many as 20 distinct genes. One of the clinical variants, recessive dystrophic EB (RDEB), demonstrates sub-lamina densa blistering accompanied by alterations in anchoring fibrils due to mutations in COL7A1. In this study, we characterized a patient with widespread connective tissue abnormalities, including skin blistering similar to that in RDEB. Whole exome sequencing, combined with genome-wide homozygosity mapping, identified a homozygous missense mutation in PLOD3 encoding lysyl hydroxylase 3 (LH3). No mutations in COL7A1, the gene previously associated with RDEB, were detected. The level of LH3 was dramatically reduced in the skin and fibroblast cultures from the patient. The blistering in the skin occurred below the lamina densa and was associated with variable density and morphology of anchoring fibrils. The level of type VII collagen expression in the skin was markedly reduced. Analysis of hydroxylysine and its glycosylated derivatives (galactosyl-hydroxylysine and glucosyl-galactosyl-hydroxylysine) revealed marked reduction in glycosylated hydroxylysine. Collectively, these findings indicate that PLOD3 mutations can result in a dystrophic EB-like phenotype in the spectrum of connective tissue disorders and add it to the list of candidate genes associated with skin fragility.

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