High frequency of the 425AG splice-site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosa

Abstract

High recurrence of the splice-site mutation 425A-->G in central European patients with DEB should be taken into account when designing COL7A1 mutation detection strategies. Reporting of three novel COL7A1 mutations in this study further emphasizes the molecular heterogeneity of DEB and provides more information for studies on genotype-phenotype correlations in different DEB subtypes.

Pregnancy after PGD for recessive dystrophic epidermolysis bullosa inversa: genetics and preimplantation genetics

“…This mutation represents a splice-site mutation described in central European patients with DEB [18]. This confirmed the son's status of compound heterozygote.…”

“…Recently, van den Akker et al [8] have proposed a recessive arginine and glycine substitution in the triple helix domain of ColVII as a predominant mutation. The study of Csikós et al [18] suggests that the prevalent mutation c.425A>G is inherited in a recessive manner, and the phenotype is determined by the second mutation. In this sense, the second mutation (c.6205C>T) affects residue number 2069 of the protein that falls within subdomain COL12, considered crucial for the function of collagen VII [5].…”

“…Dental aplasia, nail dystrophy, inguinal blistering, healing with atrophy, and milia were other traits. Genetically, these children were compound heterozygotes for two point mutations, c.6205C>T and c.425A>G. In particular, c.425A>G was described as a prevalent mutation causing DEB in central Europe [18]. This mutation was screened in the affected child because of his geographical origin (Romania).…”

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].…”

Analysis of the COL7A1 gene in Czech patients with dystrophic epidermolysis bullosa reveals novel and recurrent mutations

“…The most common mutation was the transition c.425A>G. This mutation was detected in 10 probands in a heterozygous state, and in 3 probands in a homozygous state (29.6% of mutant alleles). In the study of Csikos et al [4], COL7A1 mutations were analysed in 43 unrelated patients with DEB phenotypes from the registries of DEBRA Hungary and DEBRA Germany and the mutation c.425A>G was identified in 10 of them (11 of 86 alleles, 12.8%). The transition c.425A>G at the À2 donor splice site of exon 3 cause aberrant splicing and at least two abnormal transcripts with premature termination codons are generated downstream of this mutation [5].…”