Detection of a new pathogenic mutation on COL۷A۱ gene associated with autosomal recessive Dystrophic Epidermolysis Bullosa

Background and Aim: Dystrophic Epidermolysis Bullosa (DEB) as one of the major types of epidermolysis bullosa is a genetic skin disorder that encompasses a wide range of signs and symptoms. It is generally manifested by severe blistering, aplasia/hypoplasia of the skin, cheilitis, and dystrophic nails. DEB is caused by genetic defects in the COL۷A۱ gene and may be inherited in an autosomal dominant (DDEB) or autosomal recessive (RDEB) form depending on the subtype. Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of DEB that begins at birth and determined by recurrent blistering at the level of the sublamina densa below the cutaneous basement membrane. In the present study, we evaluate a patient with a new pathogenic mutation on the COL۷A۱ gene, which is associated with RDEB.Methods: The study is including a ۱۴-year-old symptomatic boy referred to the Dr. Mohaddes Medical Genetics Laboratory (DMMGL). His symptoms started with the fusion of fingers and toes, loss of nails, and blistering of the hands and feet. Blood Sample was collected from the patient and after DNA extraction, target regions captured with Nimblegen chip in the genes causing Epidermolysis Bullosa(۱۴۴۵ monogenic disease) followed by Next Generation Sequencing. Detected variations were then validated using Q-PCR.Results: One mutation c.۷۲۳۴C>T(p.Arg۲۴۱۲Ter; Hom) on the COL۷A۱ gene has been detected in homozygous status. The mutation has been reported for its pathogenicity. Its frequencies in the normal population are very low. COL۷A۱-related Dystrophic Epidermolysis Bullosa is inherited in an autosomal dominant/recessive manner. The inheritance pattern of disease in the current patient showed an autosomal recessive pattern. The point mutation leads to alteration in the sequence of amino acids, which is expected to affect the protein’s function. We detected this mutation in patient’s parents in heterozygous status.Conclusion: The c.۷۲۳۴C>T(p.Arg۲۴۱۲Ter; Hom) mutation on the COL۷A۱ gene has a pathogenic effect on collagen VII protein structure.

کلیدواژه ها:

Dystrophic Epidermolysis Bullosa (DEB) ، COL۷A۱ gene ، Collagen VII ، Pathogenic Mutation ، Next Generation Sequencing (NGS)