title: Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa.
abstract: The inherited mechanobullous disease, dystrophic epidermolysis bullosa, is caused by type VII collagen gene (COL7A1) mutations. We studied six unrelated patients with a distinct clinical subtype of this disease, epidermolysis bullosa pruriginosa, characterized by pruritus, excoriated prurigo nodules, and skin fragility. Mutation analysis using polymerase chain reaction amplification of genomic DNA, heteroduplex analysis and direct nucleotide sequencing demonstrated pathogenetic COL7A1 mutations in each case. Four patients had a glycine substitution mutation on one COL7A1 allele (G1791E, G2242R, G2369S, and G2713R), a fifth was a compound heterozygote for a splice site mutation (5532 + 1G-to-A) and a single base pair deletion (7786delG), and a sixth patient was heterozygous for an out-of-frame deletion mutation (6863del16). This study shows that the molecular pathology in patients with the distinctive clinical features of epidermolysis bullosa pruriginosa is heterogeneous and suggests that other factors, in addition to the inherent COL7A1 mutation(s), may be responsible for an epidermolysis bullosa pruriginosa phenotype.
authors.affiliation: Department of Cell and Molecular Pathology, St John's Institute of Dermatology (The Guy's, King's College and St Thomas' Hospitals' Medical School), London, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: G H
authors.initials: GH
authors.lastname: Ashton
authors.forename: R
authors.initials: R
authors.lastname: Mohammedi
authors.forename: C C
authors.initials: CC
authors.lastname: Lyon
authors.forename: B
authors.initials: B
authors.lastname: Kirby
authors.forename: K E
authors.initials: KE
authors.lastname: Harman
authors.forename: J C
authors.initials: JC
authors.lastname: Salas-Alanis
authors.forename: D J
authors.initials: DJ
authors.lastname: Atherton
authors.forename: P V
authors.initials: PV
authors.lastname: Harrison
authors.forename: W A
authors.initials: WA
authors.lastname: Griffiths
authors.forename: M M
authors.initials: MM
authors.lastname: Black
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D020029:Base Pairing; D003094:Collagen / Q000235:genetics*; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics*; D005091:Exons; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011537:Pruritus / Q000235:genetics; D015183:Restriction Mapping
chemical_list: D003094:Collagen