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Molecular Basis of Recessive Dystrophic Epidermolysis Bullosa: Genotype/Phenotype Correlation in a Case of Moderate Clinical Severity
- Source :
- Journal of Investigative Dermatology. (1):119-124
- Publisher :
- The Society for Investigative Dermatology, Inc. Published by Elsevier Inc.
-
Abstract
- Mutations within the gene encoding the anchoring fibril protein type VII collagen (COL7A1) have recently been established as the pathogenetic basis for the inherited blistering skin disorder, dystrophic epidermolysis bullosa. We report a patient with a moderately severe phenotype of recessive dystrophic epidermolysis bullosa. We report a patient with a moderately severe phenotype of recessive dystrophic epidermolysis bullosa, in whom COL7A1 mutations have been identified on both alleles. The patient is a 5-y-old Japanese male of nonconsanguineous parents, with clinical features including generalized trauma-induced blistering since birth, complete loss of nails, and partial fusion of the fingers and toes. Immunofluorescence microscopy examination of the dermal-epidermal junction in the patient's skin revealed near-normal intensity staining with an antitype VII collagen antibody (LH7:2). Transmission electron microscopy showed a reduced number of thin, poorly-formed anchoring fibrils. PCR amplification of genomic DNA, followed by heteroduplex analysis, and nucleotide sequencing demonstrated that the patient was a compound heterozygote for a nonsense mutation (E2858X) within the NC-2 domain of type VII collagen and a missense mutation (G2576R) within the type VII collagen triple helix. Both mutations were verified by restriction endonuclease digestion. Information about these mutations advances our understanding of genotype-phenotype correlations in dystrophic epidermolysis bullosa, and further delineates the mechanisms involved in dermal-epidermal dysadhesion.
- Subjects :
- Male
Genotype
Nonsense mutation
Molecular Sequence Data
Genes, Recessive
Dermatology
Biology
Compound heterozygosity
Biochemistry
Anchoring fibrils
Missense mutation
Humans
Allele
mutation detection in genodermatoses
Gene
Molecular Biology
Skin
type VII collagen mutations
Base Sequence
integumentary system
Cell Biology
Molecular biology
Epidermolysis Bullosa Dystrophica
Restriction enzyme
Microscopy, Electron
Phenotype
Child, Preschool
Mutation
molecular genetics of EB
inheritable blistering diseases
Heteroduplex
Subjects
Details
- Language :
- English
- ISSN :
- 0022202X
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....03440e3b0524570917bcb2bb2c9e6652
- Full Text :
- https://doi.org/10.1111/1523-1747.ep12329600