Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the type VII collagen gene (COL7A1). In this study, we assessed the molecular basis of recessive DEB in five affected individuals from two Mexican families. Both fathers of the affected children were first cousins. Genomic DNA was extracted from peripheral blood samples and assessed for COL7A1 mutations by polymerase chain reaction (PCR) amplification, heteroduplex analysis and direct automated sequencing of PCR products displaying heteroduplex bandshifts. In one family, we identified a homozygous 1 bp insertion of a G nucleotide in exon 19 of COL7A1, designated 247OinsG, in three affected sisters. This mutation causes a frameshift and a premature termination codon on both alleles 178 bp downstream from the insertion; both parents were shown to be heterozygous carriers of this mutation. In the second family, the father of the other two affected children was also found to be a heterozygous carrier of this frameshift mutation. In addition, his unrelated partner was shown to be a heterozygous carrier of a different COL7A1 frameshift mutation, an insertion of a T nucleotide in exon 32, designated 3948insT. This mutation also results in a premature termination codon, 126 bp downstream from the insertion. Both affected children were compound heterozygotes for the 2470insG/3948insT mutations in COL7A1. Overall, these molecular findings offer a genetic explanation for the skin fragility in these related Mexican patients with recessive DEB. Immediate benefits from elucidation of the mutations include assessment of carrier status in other members of the family and the feasibility of DNA-based prenatal testing in subsequent pregnancies.
Salas-Alanis, J. C., Mellerio, J. E., Amaya-Guerra, M., Ashton, G. H. S., Eady, R. A. J., & McGrath, J. A. (1998). Frameshift mutations in the type VII collagen gene (COL7A1) in five Mexican cousins with recessive dystrophic epidermolysis bullosa. British Journal of Dermatology, 852-858. https://doi.org/10.1046/j.1365-2133.1998.02225.x