<i>COL7A1</i> Recessive Mutations in Two Siblings with Distinct Subtypes of Dystrophic Epidermolysis Bullosa: Pruriginosa versus Nails Only

Abstract

Dystrophic epidermolysis bullosa (DEB) is a rare, clinically heterogeneous, blistering genodermatosis inherited as either autosomal dominant or recessive trait. All DEB forms are caused by mutations in the COL7A1 gene, which encodes for type VII collagen, the major component of the anchoring fibrils ensuring epithelial-mesenchymal adhesion. Major determinants of clinical heterogeneity in DEB are COL7A1 mutation types and their consequences at mRNA and protein levels; nevertheless, siblings with the same genetic alterations can manifest highly variable clinical signs. Here, we report novel compound heterozygous recessive COL7A1 missense mutations in 2 siblings presenting different DEB clinical subtypes. Our findings document the rare occurrence of recessive inheritance for the nails only DEB variant and emphasize the role of acquired phenotype-modifying factors in DEB pruriginosa pathogenesis.

Identical COL71A1 heterozygous mutations resulting in different dystrophic epidermolysis bullosa phenotypes

“…No clear pattern has emerged from attempts to correlate COL7A1 gene mutations with disease phenotype, and our three cases support this . As previously reported, identical mutations, dominant or recessive, have been found in patients with different subtypes of DEB, ranging from nails‐only disease to DEB‐Pr …”

“…7,8 As previously reported, identical mutations, dominant or recessive, have been found in patients with different subtypes of DEB, ranging from nails-only disease to DEB-Pr. 9,10 Type VII collagen is composed of three identical alpha chains with a central collagenous domain flanked by an amino terminus and a carboxyl terminus. Exons 29-112, 2-28 and 113-118 encode these three regions.…”

Aplasia cutis congenita with dystrophic epidermolysis bullosa: clinical and mutational study

“…Among the 15 patients with the milder DEB phenotypes, one (patient 12) is homozygous for a glycine substitution and 12 were heterozygous for a missense mutation involving a glycine substitution in nine cases, an arginine or a serine substitution in two cases. These substitutions exerted a dominant effect in DDEB patients 8-11, while in compound heterozygous patients they acted synergistically with a mutation resulting in a downstream PTC (patients 16,20,21,22), a splice-site mutation (patients 15 and 18) or a glycine substitution (patient 13). In patient 19, only the paternal/maternal PTC mutation was found.…”

“…Particular attention should also be brought to the possible contribution of epigenetic factors to the sporadic occurrence of ACC even within the same DEB kindred. Indeed, the influence of epigenetics in the clinical DEB outcome has previously been documented in DEB families with individuals presenting distinct phenotypes …”

“…Indeed, the influence of epigenetics in the clinical DEB outcome has previously been documented in DEB families with individuals presenting distinct phenotypes. 21,22…”