title: Identification of novel type VII collagen gene mutations resulting in severe recessive dystrophic epidermolysis bullosa.
abstract: In this work, we studied the proband in a small nuclear family of Chinese and Dutch/German descent and identified two novel mutations in the type VII collagen gene leading to recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens variant (HS-RDEB). The maternal mutation is a single base pair deletion of a cytosine nucleotide in exon 26, designated 3472delC, resulting in a frameshift and a premature termination codon (PTC) within the same exon, 7 bp downstream of the site of the mutation. The paternal mutation is a G-->A transition located at the 5' donor splice site within intron 51, designated IVS51 + 1G-->A. This mutation leads to the activation of a cryptic splice site, 32 bp downstream of the mutation site and to subsequent aberrant out-of-frame splicing, resulting in two alternative mRNA transcripts and a downstream PTC. To our knowledge, these two mutations have not been previously reported. These findings extend the body of evidence for compound heterozygous mutations leading to HS-RDEB and provide the basis for prenatal diagnosis in this family.
authors.affiliation: Department of Dermatology, Columbia University, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Massé
authors.forename: P B
authors.initials: PB
authors.lastname: Cserhalmi-Friedman
authors.forename: V
authors.initials: V
authors.lastname: Falanga
authors.forename: J T
authors.initials: JT
authors.lastname: Celebi
authors.forename: A
authors.initials: A
authors.lastname: Martinez-Mir
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D001483:Base Sequence; D024143:Collagen Type VII / Q000235:genetics*; D004252:DNA Mutational Analysis; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000473:pathology; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D024143:Collagen Type VII