The first COL7A1 mutation survey in a large Spanish dystrophic epidermolysis bullosa cohort: c.6527insC disclosed as an unusually recurrent mutation

Abstract

Although the COL7A1 database indicates that most DEB mutations are family specific, the pathogenic mutation c.6527insC was highly recurrent in our cohort. This level of recurrence for a single genetic defect has never previously been reported for COL7A1. Our findings are essential to the clinicians caring for patients with DEB in Spain and in the large population of Spanish descendants in Latin America. They also provide geneticists a molecular clue for a priority mutation screening strategy.

The international dystrophic epidermolysis bullosa patient registry: An online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations

“…Although a few recurrent mutations have been identified in several populations due to founder effects [Csikós et al, 2005;Escámez et al, 2010;Gardella et al, 2002;Jeřábková et al, 2010;Kern et al, 2006;Mellerio et al, 1997;Mohammedi et al, 1999;Murata et al, 2004;Salas-Alanis et al, 2000;Tamai et al, 1999], most families carry unique mutations, explaining the large number of different mutations identified so far. Most dominant mutations can cause heterogeneous phenotypes [Mellerio et al, 1998], while the clinical consequences for recessive mutations depend on the exact constellation of the genotype, in which the least "severe" mutation usually determines the phenotype Dunnill et al, 1996;Winberg et al, 1997].…”

“…The relative type VII collagen deposition at the basement membrane zone, and the number and ultra-structure of anchoring fibrils can be assessed by immunofluorescence (IF) and electron microscopy (EM) techniques, respectively. Genotype-phenotype correlation has been extensively studied for the major subtypes of DEB [Abu Sa'd et al, 2006;Almaani et al, 2011;Dang et al, 2007;Escámez et al, 2010;Fine et al, 2008;Gardella et al, 2002;Hovnanian et al, 1997;Jeřábková et al, 2010;Kern et al, 2006Kern et al, , 2009Ouragini et al, 2010;Salas-Alanis et al, 2000;Sawamura et al, 2005;Van den Akker et al, 2009;Varki et al, 2007]. These studies have revealed that severe generalized RDEB is generally caused by bi-allelic mutations that result in a premature termination codon (PTC) (i.e., nonsense mutations, frame-shifting deletions, insertions/duplications, indels, and certain splice-site mutations).…”

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

“…According to the current classification of inherited EB, the nails-only phenotype is considered a very rare autosomal dominant DEB variant probably overlooked because of negligible clinical implications [1,15,16,17,18]. Indeed, patients with this condition have been frequently disclosed as heterozygous carriers for a dominant mutation in pedigrees where other members with overt skin blistering resulted from compound heterozygous dominant and recessive glycine substitution mutations [19,20].…”

Novel and recurrent COL7A1 mutations in Chilean patients with dystrophic epidermolysis bullosa

“…While the former was previously described [6], the latter is a novel COL7A1 mutation. Allele frequencies of recurrent mutations were 42% (50/120) for c.6527dupC and 28% (34/120) for c.7708delG.…”