Scientists have discovered a new mutation in the COL7A1 gene — which provides instructions for making a type of collagen protein — in a Chinese family with pretibial dystrophic epidermolysis bullosa (DEB), a study revealed.
The study, “A novel mutation of COL7A1 in a Chinese DEB‐Pt family and review of the literature,” was published in the Journal of Cosmetic Dermatology.
Pretibial DEB is a very rare subtype of dystrophic epidermolysis bullosa. It is characterized by itching, blistering, and scarring, predominantly in the pretibial region, which is located on the front of the lower legs.
Blisters develop due to structural defects in type VII collagen, the most abundant protein in the skin, which is responsible for holding its layers together.
More than 730 mutations have been identified in the COL7A1 gene, which provides instructions to make type VII collagen, across different subtypes of DEB.
To better understand which mutations cause pretibial DEB, the researchers analyzed the genetic sequence of a group of relatives with this disorder.
The first person diagnosed (proband) was a 23-year-old woman from Anhui Province in China. Since birth, her pretibial area had been prone to blisters after rubbing or squeezing, which was followed by scattered miliary rash — a rash that resembles millet seeds — and itching.
Despite use of topical medications, the patient did not experience clear lessening of her symptoms.
As the disease progressed, the rash gradually expanded to the back of the foot, which was accompanied by ankle swelling. Although the woman had no family history of other hereditary diseases, five other family members developed similar symptoms, but with diverse severity and prognosis.
The lesions were most severe in the patient’s father, and mildest in her younger sister, who did not have skin lesions. By the time the study was concluded, the father had serious miliary rash and blisters on the back waist and limbs.
To learn more, the team conducted whole exome sequencing in DNA samples. This approach focuses on the small bits of DNA (exons) that provide instructions to make protein.
The results showed the same previously unreported mutation in COL7A1 in all affected family members. This variant, known as p.Gly2287Glu, is a missense mutation, which refers to changes in the building blocks of DNA (nucleotides) leading to a different amino acid. Specifically, this mutation was located in exon 87.
“The discovery of the new mutation extends the COL7A1 mutation database,” the scientists said. “This will facilitate the molecular diagnosis, treatment, and prognosis of [pretibial DEB].”
The finding is in line with current literature, the researchers said, as most mutations associated with pretibial DEB are located in the exons of COL7A1 and are of the missense subtype.
As for the diverse severity of clinical manifestations in this family, the team said it may be related to environmental factors or levels of other proteins in the skin, aside from type VII collagen.
Further research is required, the scientists said. However, the very small number of people with pretibial DEB complicates studies of how the genetic profile leads to disease manifestations.