Genotype–Phenotype Correlation in Chinese Patients with Dystrophic Epidermolysis Bullosa Pruriginosa

Abstract

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare variant of dystrophic epidermolysis bullosa (DEB) due to dominant or recessive mutations in the COL7A1 gene. More than 40 mutations in COL7A1 have been described in DEB-Pr. The aim of this study was to understand the genotype-phenotype correlation in Chinese patients with DEB-Pr. Three Chinese families with typical clinical features of DEB-Pr were studied. The results were analysed in association with the eight Chinese DEB-Pr patients reported in the literature. In the three Chinese families with DEB-Pr, we found two dominant cases with G1773R and c.6900+1G>C mutations, and one case with heterozygous G2701W mutation of uncertain inheritance mode. In the 10 Chinese patients with dominant type of DEB-Pr, 7 glycine substitutions and three splicing site mutations of exon 87 skipping were identified. Glycine substitution mutations in the triple helix region and exon 87 skipping, leading to the in-frame deletion of 23 amino acid residues in the triple-helix, are often seen in Chinese patients with dominant DEB-Pr, although the glycine substitutions are also frequently present in dominant DEB.

Four novel and two recurrent glycine substitution mutations in theCOL7A1gene in Chinese patients with epidermolysis bullosa pruriginosa

“…To date, including this study, there have been 52 mutations in the COL7A1 gene reported in association with EBP, of which 35 mutations are glycine substitutions in the first amino acid of the Gly–X–Y repeats located in the triple‐helix region, indicating that glycine substitution is the most common mutations underlying EBP. The recurrent mutation p.G2287R in patient 2 (FEBP) was initially reported in a patient with recessive dystrophic EB, whereas that patient's mother, the heterozygous carrier of this mutation, presented only with nail deformity restricted to the great toes .…”

“…In our second case, all the affected family members carrying the p.G2287R mutation developed moderate to serious prurigo‐like lesions and pruritus during the third decade of life. Another recurrent mutation, p.G2701W, which was detected in patient 6 (SEBP) was recently reported in a female Chinese patient with EBP, whose clinically unaffected mother carried the same mutation . In that study, the author was unable to exclude the possibility of recessive inheritance of the mutation p.G2701W.…”

Epidermolysis bullosa pruriginosa: A case with a novel mutation and co-existent lichen amyloidosus

“…[3][4][5][6][7][8][9] Comparing dystrophic epidermolysis bullosa and epidermolysis bullosa pruriginosa, there is generally no clear genotype-phenotype correlation although skipping of exon 87 in the COL7A1 gene can be associated with the dominantly-inherited form of epidermolysis bullosa pruriginosa. [7][8][9] The novel dominant-negative heterozygous acceptor splice site mutation in the COL7A1 gene (IVS67-1G>T) was found in both our patient and his youngest son, who was 34 years old at the time of testing. The latter can reasonably be assumed to be at risk of developing epidermolysis bullosa pruriginosa in the future and should receive treatment as soon as symptoms arise.…”

Case Report Novel and recurrent COL7A1 mutations in Chinese patients with dystrophic epidermolysis bullosa pruriginosa

“…DEB-Pr, a rare subtype of DEB, also shows genetic heterogeneity, as autosomal dominant and recessive inheritance patterns have been previously reported (Jiang et al, 2012). COL7A1 gene mutations have been demonstrated to cause the entity (Christiano et al, 1997).…”

“…Theoretically, COL7A1 gene mutations can influence the biosynthesis of collagen VII, resulting in different phenotypes of DEB-Pr (Drera et al, 2006;Dang and Murrell, 2008). Furthermore, although additional immune-mediated factors may be involved in the pathogenesis of DEB-Pr (Jiang et al, 2012), it is unclear whether other genetic, epigenetic, metabolic, or environmental factors contribute to the DEB-Pr phenotype (Almaani et al, 2009). …”