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Identification of novel type VII collagen gene mutations resulting in severe recessive dystrophic epidermolysis bullosa
Author(s) -
Massé M.,
CserhalmiFriedman P. B.,
Falanga V.,
Celebi J. T.,
MartinezMir A.,
Christiano A. M.
Publication year - 2005
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/j.1365-2230.2005.01763.x
Subject(s) - exon , splice site mutation , frameshift mutation , genetics , mutation , epidermolysis bullosa , intron , biology , compound heterozygosity , rna splicing , exon skipping , proband , transition (genetics) , microbiology and biotechnology , epidermolysis bullosa dystrophica , gene , alternative splicing , rna
Summary 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.