Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance
Journal Article
·
· American Journal of Human Genetics
OSTI ID:285047
- Thomas Jefferson Univ., Philadelphia, PA (United States)
- National Skin Centre (Singapore)
The dystrophic forms of epidermolysis bullosa (DEB) are characterized by fragility of the skin and mucous membranes. DEB can be inherited in either an autosomal dominant or autosomal recessive pattern, and the spectrum of clinical severity is highly variable. The unifying diagnostic hallmark of DEB is abnormalities in the anchoring fibrils, which consist of type VII collagen, and recently, mutations in the corresponding gene, COL7A1, have been disclosed in a number of families. In this study, we report six families with glycine substitution mutations in the triple-helical region of type VII collagen. Among the six families, two demonstrated a mild phenotype, and the inheritance of the mutation was consistent with the dominantly inherited form of DEB. In the four other families, the mutation was silent in the heterozygous state but, when present in the homozygous state, or combined with a second mutation, resulted in a recessively inherited DEB phenotype. Type VII collagen is, therefore, unique among the collagen genes, in that different glycine substitutions can be either silent in heterozygous individuals or result in a dominantly inherited DEB. Inspection of the locations of the glycine substitutions along the COL7A1 polypeptide suggests that the consequences of these mutations, in terms of phenotype and pattern of inheritance, are position independent. 29 refs., 4 figs., 2 tabs.
- OSTI ID:
- 285047
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 4 Vol. 58; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
Similar Records
Compound heterozygosity for COL7A1 mutations in twins with dystrophic epidermolysis bullosa: A recessive paternal deletion/insertion mutation and a dominant negative maternal glycine substitution result in a severe phenotype
Premature termination codons in the Type VII collagen gene (COL7A1) underlie severe, mutilating recessive dystrophic epidermolysis bullosa
PCR-SSCP analysis of the type VII collagen gene (COL7A1): Detection of a point mutation in five patients
Journal Article
·
Sun Mar 31 23:00:00 EST 1996
· American Journal of Human Genetics
·
OSTI ID:285048
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)
·
OSTI ID:6792707
PCR-SSCP analysis of the type VII collagen gene (COL7A1): Detection of a point mutation in five patients
Journal Article
·
Thu Sep 01 00:00:00 EDT 1994
· American Journal of Human Genetics
·
OSTI ID:134202