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
| Autor: | H I Szocs, Sarolta Kárpáti, Attila Horváth, A Lászik, Márta Csikós, S. Mecklenbeck, Leena Bruckner-Tuderman |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Collagen Type VII Adolescent DNA Mutational Analysis Molecular Sequence Data Dermatology Biology Polymerase Chain Reaction Genotype Humans Allele Child Gene Skin Genetics Splice site mutation Base Sequence Epidermolysis Bullosa Dystrophica Pedigree Europe Restriction enzyme Phenotype Child Preschool Mutation (genetic algorithm) Mutation Mutation testing Female RNA Splice Sites Epitope Mapping Heteroduplex |
| Zdroj: | The British journal of dermatology. 152(5) |
| ISSN: | 0007-0963 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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