Weber-Cockayne Type Epidermolysis Bullosa Simplex Resulting from a Novel Mutation (c. 608T>C) in the Keratin 5 Gene

Epidermolysis bullosa simplex (EBS), an inherited genetic disorder, is most often caused by a dominant-negative mutation in either the keratin 5 (KRT5) or the keratin 14 (KRT14) gene. These keratin mutants result in a weakened cytoskeleton and cause extensive cytolysis. It is important to analyze the KRT5 or KRT14 genes of the patient and their family members by mutational analysis in order to identify genetic defects as well as the need for genetic counseling. In this study, we present a 5-year-old Korean boy who had been developing blisters and erosions on the palms of his hands and soles of his feet since infancy. In addition, while his younger sister and father showed similar clinical manifestation, his mother did not. The patient was diagnosed with EBS based on clinical manifestation, which is characterized by the presence of blisters restricted to the palms and soles, histological findings, and mutational analysis. Mutational analysis of the patient's DNA revealed a thymine-to-cytosine transition at codon 608 in the KRT-5 gene, resulting in a leucine-to-proline substitution in the keratin 5 protein. The same mutation was identified in the paternal, but not maternal, DNA. Here, we report a case of Weber-Cockayne type EBS with vesicles and bullae restricted to the palms and soles with a novel, paternally inherited mutation in KRT5 gene (exon2, c.608T>C).

Type VII Collagen Gene Mutations (c.8569G>T and c.4879G>A) Result in the Moderately Severe Phenotype of Recessive Dystrophic Epidermolysis Bullosa in a Korean Patient

Dystrophic epidermolysis bullosa (DEB) are caused by mutations in the COL7A1 gene, which encodes type VII collagen. Even though more than 500 different COL7A1 mutations have been identified in DEB, it still remains to be under-investigated. To investigate the mutation of COL7A1 in moderately severe phenotype of recessive DEB (RDEB) in a Korean patient, the mutation detection strategy was consisted of polymerase chain reaction (PCR) amplification of genomic DNA, followed by heteroduplex analysis, nucleotide sequencing of the PCR products demonstrating altered mobility. In this study, we found that one mutation (c.8569G>T) was detected within exon 116. The mutation of c.8569G>T in exon 116 changed the GAG (Glu) to TAG, eventually resulted in premature termination of type VII collagen polypeptide. Furthermore the mother did not have the mutation c.8569G>T in exon 116. The other novel mutation (c.4879G>A) was detected within exon 51 of both patient and mother, thereby resulting in changing valine (Val) to isoleucine (Ile) in type VII collagen polypeptide. Taken together, in this study we identified compound heterozygosity for COL7A1 mutations (c.8569G>T and c.4879G>A) in moderately severe RDEB in a Korean patient. We hope that this data contribute to the expanding database on COL7A1 mutations in DEB.