2 Gene Mutations Identified as Possible Cause of EBS in One Patient, Researchers Say

Researchers found two mutations in a gene that carries the instructions for the protein plectin in a patient with epidermolysis bullosa simplex (EBS).

Plectin helps maintain the integrity of the skin, and the research team believes the mutations they found might be the cause of the disease in this patient.

The study, “Loss of interaction between plectin and type XVII collagen results in epidermolysis bullosa simplex,” was published in the journal Human Mutation, and reports the case of a Japanese boy with EBS. A healthy volunteer was also examined.

In humans, there are generally two copies of each gene, called alleles (one inherited from the mother and one from the father). One mutation in each of the plectin alleles was found in the patient studied.

One of the mutations would be expected to stop the allele’s activity altogether, resulting in no production of the plectin protein. The other mutation found would allow for the production of plectin protein, but is suspected of interfering with the binding of plectin to another protein called type XVII collagen (COL17).

Both plectin and COL17 are important proteins for skin integrity.

EB is a group of diseases caused by improper function of the basement membrane zone (BMZ), which is the tissue between the dermis and epidermis, the two layers of cells that make up the skin.

Laboratory studies have shown that the binding of plectin to COL17 helps in the formation of hemidesmosomes in the BMZ. Hemidesmosomes are structures that contribute to the attachment of epithelial cells to the underlying basement membrane in tissues like the skin.

The team suggested that disruption of hemidesmosomes due to the defective plectin gene was the cause of EB in this patient.

They found that the activity of plectin and COL17 were decreased in cells taken from the patient, compared to cells from a healthy donor.

The team also searched for mutations in other genes responsible for the production of proteins in the BMZ, but found none.

This strengthens their initial hypothesis that mutations in the plectin gene, and subsequent impairment of plectin-COL17 binding, were the cause of EBS in this particular patient.

“We demonstrate that plectin-COL17 binding helps to maintain epidermal BMZ organization,” the researchers wrote, adding that a “disrupted interaction between plectin and COL17 is involved in the development of EB.”

“Our study suggests that protein-protein binding defects may underlie EB in patients with unidentified disease-causing sequence variants,” the team concluded.