title: Analysis of the COL17A1 in non-Herlitz junctional epidermolysis bullosa and amelogenesis imperfecta.
abstract: Non-Herlitz junctional epidermolysis bullosa (nH-JEB) disease manifests with skin blistering, atrophy and tooth enamel hypoplasia. The majority of patients with nH-JEB harbor mutations in COL17A1, the gene encoding type XVII collagen. Heterozygotes with a single COL17A1 mutation, nH-JEB defect carriers, may exhibit only enamel hypoplasia. In this study, to further elucidate COL17A1 mutation phenotype/ genotype correlations, we examined two unrelated families with nH-JEB. Furthermore, we hypothesized that COL17A1 mutations might underlie or worsen the enamel hypoplasia seen in amelogenesis imperfecta (AI) patients that are characterized by defects in tooth enamel formation without other systemic manifestations. We therefore conducted COL17A1 mutational analysis in three patients from two AI families. One nH-JEB patient showed no COL17A1 expression and was a compound heterozygote for the novel premature termination codon (PTC) mutations 1285delA and Q1387X. In addition, reduced COL17A1 expression was found in a second nH-JEB patient who was homozygous for the novel PTC mutation 4335delC, the most carboxyl terminal PTC mutation thus far identified. Due to nonsense mediated mRNA decay, the position of these PTC mutations is thought not to influence the effect of COL17A1 transcript loss and hence the severity of the nH-JEB phenotype. This study is the first to suggest that type XVII collagen carboxyl PTC mutations lead to restoration of truncated polypeptide expression and to a milder clinical disease severity in nH-JEB. Conversely, we failed to detect any pathogenic COL17A1 defects in AI patients, in either exon or within the intron-exon borders of AI patients. This study furthers the understanding of mutations in COL17A1 causing nH-JEB, and clearly demonstrates that the mechanism of enamel hypoplasia differs between nH-JEB and AI diseases.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawamura
authors.forename: Maki
authors.initials: M
authors.lastname: Goto
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kida
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sakiyama
authors.forename: Koki
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D000567:Amelogenesis Imperfecta / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004820:Epidermolysis Bullosa / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D024041:Non-Fibrillar Collagens / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII