Mutation analysis of the COL7A1 gene in 4 cases of recessive dystrophic epidermolysis bullosa / 中华皮肤科杂志

ABSTRACT

Objective:To analyze gene mutations in and clinical phenotypes of 4 children with recessive dystrophic epidermolysis bullosa (RDEB) .Methods:Clinical data were collected from 4 children with RDEB, and DNA was extracted from peripheral blood samples of the children and their parents. A multi-gene panel targeting congenital epidermolysis bullosa was used for high-throughput sequencing. After identification of causative gene mutations, Sanger sequencing was performed to bidirectionally verify the mutations in the patients and their parents.Results:Genetic testing showed 8 compound heterozygous mutations in the COL7A1 gene in the 4 cases. Case 1 was diagnosed with moderate generalized RDEB, and inherited a paternal mutation c.7828C>T and a maternal mutation c.448G> A; case 2 was also diagnosed with moderate generalized RDEB, and inherited a paternal mutation c.3625_3635del and a maternal mutation c.2726_2728del; case 3 was diagnosed with localized RDEB, carrying a paternal mutation c.682+1G>A and an allelic mutation c.5532+1G>A, but the mutation c.5532+1G>A was not identified in the DNA extracted from the parental peripheral blood samples; case 4 was diagnosed with severe generalized RDEB, and inherited a paternal mutation c.5196delC and a maternal mutation c.500_501insAGGG. Among these mutations, c.2726_2728del and c.5196delC had not been reported previously.Conclusions:All the 4 children with RDEB carried compound heterozygous mutations in the COL7A1 gene, which may be the cause of RDEB. The phenotypes of biallelic frameshift mutation carriers appearred more severe than those of carriers of compound heterozygous mutations composed of biallelic splice site, missense and nonsense, frameshift and amino acid deletion or insertion mutations.