Expanding the COL7A1 Mutation Database: Novel and Recurrent Mutations and Unusual Genotype – Phenotype Constellations in 41 Patients with Dystrophic Epidermolysis Bullosa

Johannes S. Kern, Jürgen Kohlhase, Leena Bruckner-Tuderman, Cristina Has
2006 Journal of Investigative Dermatology  
Dystrophic epidermolysis bullosa (DEB), a heterogeneous hereditary skin disorder characterized by traumainduced blistering and scarring, affects thousands of families worldwide. The clinical manifestations extend from minor nail dystrophy to severe life-threatening blistering, making early molecular diagnosis and prognostication of utmost importance for the affected families. DEB is caused by mutations in the COL7A1 gene encoding collagen VII in the skin. Molecular diagnostics and
more » ... type correlations in DEB remain complex owing to the gene structure, large variety of mutations, high rate of novel mutations, complex protein structure and assembly, and the heterogeneity of phenotypes. Here, we report an efficient strategy for COL7A1 mutation detection using direct automated DNA sequencing and implementation of software tools. With this approach, COL7A1 mutations of 41 DEB families were disclosed. Twenty-four mutations were novel and two recurrent. Elucidation of biological consequences of the mutations helped define disease mechanisms, but also revealed several unusual genotypic and/or phenotypic constellations, which impeded the diagnostics and prognostication. In addition, the studies disclosed a de novo mutation in recessive DEB and two new polymorphisms in the COL7A1 gene. Abbreviations: DEB, dystrophic epidermolysis bullosa; HS-RDEB Hallopeau-Siemens recessive dystrophic epidermolysis bullosa; PTC premature termination codon; RDEB, recessive dystrophic epidermolysis bullosa; RT-PCR, reverse transcriptase-polymerase chain reaction
doi:10.1038/sj.jid.5700219 pmid:16484981 fatcat:yqizpvj5lze6jhty6wwsgbhvmi