Abstract | BACKGROUND: OBJECTIVE: To elucidate the mutations shown by two patients with DEB and understand the clinical phenotypes that they displayed. METHODS: We have characterized two patients, one affected by the severe recessive Hallopeau-Siemens variant of DEB (HS-RDEB) and the other by a milder recessive DEB form. RESULTS: In both patients we identified the R2063W missense mutation. The second mutation, in the HS-RDEB patient, was a novel 344insG, leading to a premature termination codon of translation ( PTC) in exon 3, while, in the other patient, it was a novel 4965C-->T transition, which creates a new donor splice site in exon 53. The effect of this anomalous splice site leads to the maturation of a 17-nucleotides-deleted mRNA containing a PTC. In addition to this aberrant transcript, a certain amount of full-length mRNA is also generated from the mutated pre-mRNA through splicing at the canonical site. CONCLUSIONS: In these patients therefore the severity of the phenotype depends on the second mutation. In the patient with the 344insG mutation, leading to a PTC, type VII collagen (COLVII) molecules are exclusively composed of chains containing the R2063W substitution; as a consequence, all anchoring fibrils (AF) are abnormal and the phenotype is severe. In the other patient, the 4965C-->T splicing mutation allows the synthesis of a certain quantity of normal chains and the consequent assembly of partially functional COLVII molecules and AF, thus explaining the mild phenotype.
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Authors | R Gardella, N Zoppi, G Zambruno, S Barlati, M Colombi |
Journal | The British journal of dermatology
(Br J Dermatol)
Vol. 147
Issue 3
Pg. 450-7
(Sep 2002)
ISSN: 0007-0963 [Print] England |
PMID | 12207583
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adolescent
- Adult
- Collagen Type VII
(genetics)
- DNA Mutational Analysis
- Epidermolysis Bullosa Dystrophica
(genetics, pathology)
- Female
- Genes, Recessive
- Humans
- Male
- Mutation
- Phenotype
- Skin
(ultrastructure)
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