Five Novel COL7A1 Gene Mutations in Three Chinese Patients with Recessive Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa (DEB) is an inherited skin disorder with variable severity and heterogeneous genetic involvement. Recessive DEB (RDEB) is a rare heritable blistering skin condition caused by loss-of-function mutations in the COL7A1 gene.

This study aimed to determine the genetic basis of three Chinese RDEB patients from different families and identify correlations between phenotype and genotype.

All three patients were diagnosed with RDEB based on typical phenotype. Genomic DNA from both the patients and parents was subjected to amplification of all 118 exons and flanking intron boundaries of the COL7A1 gene, followed by Sanger sequencing.

Sanger sequencing identified six mutations in the three patients: five novel mutations (c.2321_2322insCTGA in exon 18, c.5924-5927delAACG in exon 72, c.4871delC in exon 53, c.8278G>A in exon 111, and c.1A>G in exon 1) and one recurrent mutation (c.8038G>A in exon 108). The first three novel mutations resulted in a premature termination codon (PTC), the remaining two novel mutations caused a glycine substitution and a loss of the primary ATG start codon, respectively. All patients had a heterozygous PTC mutation combined with either a glycine substitution mutation in the critical triple-helical collagenous domain or a loss of the primary ATG start codon.

Our findings expand the mutation spectrum of COL7A1 leading to RDEB and confirm that the RDEB phenotype correlates with the compound heterozygous PTC mutation with a missense mutation. This study will aid the molecular diagnosis, genetic counseling and prognosis prediction of RDEB patients.