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

@article{Csiks2005HighFO,
  title={High frequency of the 425A→G splice‐site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosa},
  author={M{\'a}rta Csik{\'o}s and Hajnal Ir{\'e}n Szőcs and Andr{\'a}s L{\'a}szik and Sabine Mecklenbeck and A Horv{\'a}th and Sarolta K{\'a}rp{\'a}ti and L Bruckner-Tuderman},
  journal={British Journal of Dermatology},
  year={2005},
  volume={152}
}
Background  Mutations in the type VII collagen gene (COL7A1) are responsible for dominant and recessive forms of dystrophic epidermolysis bullosa (DEB). These mutations are usually specific for individual families; only a few cases of recurring mutations have been identified. 
Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa
TLDR
The nature of mutations in COL7A1 and their positions correlate reasonably logically with the severity of the resulting phenotypes.
Expanding the COL7A1 mutation database: novel and recurrent mutations and unusual genotype-phenotype constellations in 41 patients with dystrophic epidermolysis bullosa.
TLDR
An efficient strategy for COL7A1 mutation detection is reported using direct automated DNA sequencing and implementation of software tools, which revealed several unusual genotypic and/or phenotypic constellations, which impeded the diagnostics and prognostication in DEB.
The Molecular Basis of Dystrophic Epidermolysis Bullosa: Mutation Detection and Study of Clinical, Biochemical and Molecular Findings in 29 Patients
TLDR
Elucidation of the clinical, genetic and biological background of 29 DEB patients contributes to the EB mutation database, the understanding of the mechanisms underlying DEB and lays a basis for novel therapeutic approaches.
Novel and recurrent COL7A1 mutation in a Polish population.
TLDR
Using direct sequencing strategy, the aim of this study was to update the spectrum and frequency of COL7A1 mutations in a cohort of 42 Polish DEB patients and identify 25 different mutations, which gave a detection rate of about 88%.
Epidermolysis bullosa. II. Type VII collagen mutations and phenotype–genotype correlations in the dystrophic subtypes
TLDR
Examination of the mutation database suggested phenotype–genotype correlations, contributing to the improved subclassification of DEB with prognostic implications, and forms the basis for accurate genetic counselling and prenatal diagnosis in families at risk for recurrence.
A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families
TLDR
Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation, thus suggesting the presence of a common ancestor.
COL7A1 mutational analysis in Korean patients with dystrophic epidermolysis bullosa
Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder, characterized by mucocutaneous blistering, scarring and nail dystrophy following minor trauma. DEB is caused by
Mechanisms of natural gene therapy in dystrophic epidermolysis bullosa.
TLDR
It is concluded that revertant mosaicism is more common than previously assumed in patients with DEB, and the findings will have implications for future therapeutic strategies using the patient's naturally corrected cells as a source for cell-based therapies.
Signatures of Dermal Fibroblasts from RDEB Pediatric Patients
TLDR
The panel of primary patient-specific RDEB fibroblast lines (FEB) was created and the set of morphological features and the contraction capacity of the cells distinguished FEB from FHC, and an RT-qPCR gene expression analysis of cell lines confirmed the differential status of multiple genes while uncovering new ones.
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References

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A common insertion mutation in COL7A1 in two Italian families with recessive dystrophic epidermolysis bullosa.
TLDR
A recurrent premature termination codon mutation was detected in two apparently unrelated Italian families in different regions of the country and suggested a shared genetic background in the allele containing the mutation 497insA, suggesting that this genetic lesion may represent an ancestral mutation within the Italian gene pool.
Novel COL7A1 mutations in dystrophic forms of epidermolysis bullosa.
TLDR
To facilitate further refinement of genotype/phenotype correlations in DEB, a cohort of nine families with DEB is examined by a mutation detection strategy based on polymerase chain reaction amplification of COL7A1 genomic sequences, followed by heteroduplex scanning and direct nucleotide sequencing.
Strategy for identification of sequence variants in COL7A1 and a novel 2‐bp deletion mutation in recessive dystrophic epidermolysis bullosa
TLDR
The comprehensive method described is useful for rapid, reliable, and sensitive detection of sequence variants in COL7A1 and demonstrates the utility in mutation detection and prenatal exclusion of RDEB in a consanguineous family at risk for recurrence.
Recurrent mutations in the type VII collagen gene (COL7A1) in patients with recessive dystrophic epidermolysis bullosa.
TLDR
British patients with recessive DEB should be screened initially for these nucleotide changes by PCR amplification of genomic DNA and restriction analysis before more exhaustive screening of COL7A1.
The molecular basis of dystrophic epidermolysis bullosa in Mexico
Background Type VII collagen gene (COL7A1) mutations are the cause of dystrophic epidermolysis bullosa (DEB), but most mutations are specific to individual families, and there are limited data on the
Identification of two splicing mutations in the collagen type VII gene (COL7A1) of a patient affected by the localisata variant of recessive dystrophic epidermolysis bullosa.
TLDR
Allele-specific analysis of the transcripts has shown that the maternal mutation does not completely abolish the correct splicing of COLVII pre-mRNA, thus allowing, in the patient, the synthesis of a certain level of a functional protein.
Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation.
TLDR
The results provide evidence for at least two distinct molecular mechanisms underlying defective anchoring fibril formation in RDEB: one involving PTCs leading to mRNA instability and absence of protein synthesis, the other implicating missense mutations resulting in the synthesis of type VII collagen polypeptide with decreased stability and/or altered function.
Three homozygous PTC mutations in the collagen type VII gene of patients affected by recessive dystrophic epidermolysis bullosa: Analysis of transcript levels in dermal fibroblasts
TLDR
Evaluation of the levels of the mutated COLVII mRNAs in cultured skin fibroblasts of the patients and of their parents showed that all the mutated transcripts were expressed at consistent levels, indicating that a marked mRNA reduction is not a constant feature associated with PTC mutations in COL7A1.
Recurrent molecular abnormalities in type VII collagen in southern Italian patients with recessive dystrophic epidermolysis bullosa
TLDR
Haplotype analyses showed evidence for propagation of common ancestral mutant COL7A1 alleles for each of these recurrent mutations, which contribute significantly to understanding the nature of COL 7A1 pathology in patients from Southern Italy and in designing future approaches to mutation detection.
Identification of a glycine substitution and a splice site mutation in the type VII collagen gene in a proband with mitis recessive dystrophic epidermolysis bullosa
TLDR
This case was proved to be a recessively inherited disease and had a profound impact on the genetic counselling, because if the disease of the patient were to have had a new dominant mutation, he would have been counselled that the risk of his offspring being affected was one in two, but he could be accurately counselling that therisk of this offspring beingaffected was as low as the general population.
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