Premature termination codons in the Type VII collagen gene (COL7A1) underlie severe, mutilating recessive dystrophic epidermolysis bullosa

Journal Article · Sun May 01 00:00:00 EDT 1994 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1994.1238· OSTI ID:6792707

Christiano, A M; Uitto, J ^[1]; Anhalt, G ^[2]; Gibbons, S; Bauer, E A ^[3]

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1. Thomas Jefferson Univ., Philadelphia, PA (United States)
2. Johns Hopkins School of Medicine, Baltimore, MD (United States)
3. Stanford Univ. School of Medicine, CA (United States)

Epidermolysis bullosa (EB) is a group of heritable mechano-bullous skin diseases classified into three major categories on the basis of the level of tissue separation within the dermal-epidermal basement membrane zone. The most severe, dystrophic (scarring) forms of EB demonstrate blister formation below the cutaneous basement membrane at the level of the anchoring fibrils. Ultrastructural observations of altered anchoring fibrils and genetic linkage to the gene encoding type VII collagen (COL7A1), the major component of anchoring fibrils, have implicated COL7A1 as the candidate gene in the dystrophic forms of EB. The authors have recently cloned the entire cDNA and gene for human COL7A1, which has been mapped to 3p21. In this study, they describe mutations in four COL7A1 alleles in three patients with severe, mutilating recessive dystrophic EB (Hallopeau-Siemens type, HS-RDEB). Each of these mutations resulted in a premature termination codon (PTC) in the amino-terminal portion of COL7A1. One of the patients was a compound heterozygote for two different mutations. The heterozygous carriers showed an [approximately] 50% reduction in anchoring fibrils, yet were clinically unaffected. Premature termination codons in both alleles of COL7A1 may thus be a major underlying cause of the severe, recessive dystrophic forms of EB. 40 refs., 8 figs.

• OSTI ID: 6792707
• Journal Information: Genomics; (United States), Vol. 21:1; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
COLLAGEN
GENE MUTATIONS
HUMAN CHROMOSOME 3
GENETIC MAPPING
SKIN DISEASES
ETIOLOGY
DNA SEQUENCING
DNA-CLONING
BIOTECHNOLOGY
CHROMOSOMES
CLONING
DISEASES
DNA HYBRIDIZATION
GENETIC ENGINEERING
HUMAN CHROMOSOMES
HYBRIDIZATION
MAPPING
MUTATIONS
NUCLEIC ACID HYBRIDIZATION
ORGANIC COMPOUNDS
PROTEINS
SCLEROPROTEINS
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics