Conflicts of interest: None declared.
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
Article first published online: 28 APR 2005
British Journal of Dermatology
Volume 152, Issue 5, pages 879–886, May 2005
How to Cite
Csikós, M., Szőcs, H.I., Lászik, A., Mecklenbeck, S., Horváth, A., Kárpáti, S. and Bruckner-Tuderman, L. (2005), 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. British Journal of Dermatology, 152: 879–886. doi: 10.1111/j.1365-2133.2005.06542.x
- Issue published online: 28 APR 2005
- Article first published online: 28 APR 2005
- Accepted for publication 11 November 2004
- dystrophic epidermolysis bullosa;
- recurrent mutation;
- type VII collagen
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.
Objectives Forty-three unrelated Hungarian and German patients with different DEB phenotypes were screened for novel and recurrent COL7A1 mutations.
Methods All patients were classified based on clinical and genetic findings, skin immunofluorescent antigen mapping, and electron microscopic studies. Mutation analysis was performed by amplification of genomic DNA with polymerase chain reaction using COL7A1-specific primers, heteroduplex analysis, and direct nucleotide sequencing. Restriction endonuclease digestion was used for family screening and mutation verification.
Results In this group of patients, the splice-site mutation 425AG was observed frequently, in 11 of 86 alleles (12·8%), once in homozygous form and in nine cases in heterozygous form. One of 100 control alleles from clinically unaffected individuals also carried the mutation. We also identified three novel mutations: the 976-3CA splice-site mutation, and the 4929delT and 8441-15del20 deletions.
Conclusions High recurrence of the splice-site mutation 425AG 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.