Different phenotypes in recessive dystrophic epidermolysis bullosa patients sharing the same mutation in compound heterozygosity with two novel mutations in the type VII collagen gene

Abstract

In these patients therefore the severity of the phenotype depends on the second mutation. In the patient with the 344insG mutation, leading to a PTC, type VII collagen (COLVII) molecules are exclusively composed of chains containing the R2063W substitution; as a consequence, all anchoring fibrils (AF) are abnormal and the phenotype is severe. In the other patient, the 4965C-->T splicing mutation allows the synthesis of a certain quantity of normal chains and the consequent assembly of partially functional COLVII molecules and AF, thus explaining the mild phenotype.

Long-term follow-up of patients with recessive dystrophic epidermolysis bullosa in the Netherlands: Expansion of the mutation database and unusual phenotype–genotype correlations

“…In many patients, the classification into one of the subgroups is difficult and there appears to be a continuum in phenotypic severity [1,8,10,15]. Classification is especially difficult in newborns and infants when phenotypes have not completely evolved.…”

A Novel COL7A1 Gene Mutation in an Iranian Individual Suffering Dystrophic Epidermolysis Bullosa

“…10 Mutations in the COL7A1 gene cause both recessive and dominant forms of DEB, 3 which are different in terms of clinical manifestations and severity. 10 Currently, more than 400 mutations have been described for the mild and severe forms of DEB.…”

“…10 Mutations in the COL7A1 gene cause both recessive and dominant forms of DEB, 3 which are different in terms of clinical manifestations and severity. 10 Currently, more than 400 mutations have been described for the mild and severe forms of DEB. 11 The severest forms of RDEB are caused by mutations on both alleles that result in either null alleles or out-of-frame mutations from insertions/deletions, single-base substitutions, and splice junction alterations.…”

“…11 The severest forms of RDEB are caused by mutations on both alleles that result in either null alleles or out-of-frame mutations from insertions/deletions, single-base substitutions, and splice junction alterations. 6,10,[12][13][14][15] The severity may be related to the position of the stop codon; however, the presence of some functional protein appears to be the most important factor in ameliorating the disease severity. 16 Here we report a novel homozygous single-base deletion in the COL7A1 gene of a young girl from southwest Iran with a severe form of DEB.…”

X-Linked Ichthyosis along with Recessive Dystrophic Epidermolysis Bullosa in the Same Patient

“…Because there is a significant clinical overlap between the localized mild autosomal recessive type and the dominant form of DEB – and because ultrastructural studies are not always conclusive – precise diagnosis may require molecular analysis in the affected individual and his/her parents [21]. Several studies have shown these clinical manifestations to depend on the type of COL7A1 gene mutation [22,23]; while mild autosomal recessive forms derive from a variety of mutations leading to the expression of altered but partially functioning collagen VII molecules [24], the dominant mutations are typically caused by glycine substitutions in the COL7A1 gene promoting a dominant-negative interference with the wild-type protein [25]. It is known that most cases of mild-to-moderate severity correspond to recessive mutations [23,26], but genetic testing is mandatory for an accurate genetic counseling.…”