Different phenotypes in recessive dystrophic epidermolysis bullosa patients sharing the same mutation in compound heterozygosity with two novel mutations in the type VII collagen gene

✍ Scribed by R. Gardella; N. Zoppi; G. Zambruno; S. Barlati; M. Colombi

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 300 KB
• Volume: 147
• Category: Article
• ISSN: 0007-0963
• DOI: 10.1046/j.1365-2133.2002.04914.x

✦ Synopsis

Background:

Dystrophic epidermolysis bullosa (deb) is a bullous skin disease caused by mutations in the type vii collagen gene (col7a1).

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.