Human Molecular Genetics, Vol 6, 1125-1135, Copyright © 1997 by Oxford University Press
JO Winberg, N Hammami-Hauasli, O Nilssen, I Anton-Lamprecht, SL Naylor, K Kerbacher, M Zimmermann, P Krajci, T Gedde-Dahl Jr and L Bruckner-Tuderman
Dystrophic epidermolysis bullosa (EBD) is a clinically heterogeneous skin
disorder, characterized by abnormal anchoring fibrils (AF) and loss of
dermal-epidermal adherence. EBD has been linked to the COL7A1 gene at
chromosome 3p21 which encodes collagen VII, the major component of the AF.
Here we investigated two unrelated EBD families with different clinical
phenotypes and novel combinations of recessive and dominant COL7A1
mutations. Both families shared the same recessive heterozygous 14 bp
deletion at the exon-intron 115 boundary of the COL7A1 gene. The deletion
caused in-frame skipping of exon 115 and the elimination of 29 amino acid
residues from the pro-alpha1(VII) polypeptide chain. As a result,
procollagen VII was not converted to collagen VII and the C-terminal NC-2
propeptide which is normally removed from the procollagen VII prior to
formation of the anchoring fibrils was retained in the skin. All affected
individuals also carried missense mutations in exon 73 of COL7A1 which lead
to different glycine- to-arginine substitutions in the triple-helical
domain of collagen VII. Combination of the deletion mutation with a G2009R
substitution resulted in a mild phenotype. In contrast, combination of the
deletion with a G2043R substitution led to a severe phenotype. The G2043R
substitution was a de novo mutation which alone caused a mild phenotype.
Thus, different combinations of dominant and recessive COL7A1 mutations can
modulate disease activity of EBD and alter the clinical presentation of the
patients.
ARTICLES
Modulation of disease severity of dystrophic epidermolysis bullosa by a splice site mutation in combination with a missense mutation in the COL7A1 gene
Biochemistry Department, Institute of Medical Biology, University of Tromso, Norway. janow@fagmed.uit.no
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Hammami-Hauasli, H. Schumann, M. Raghunath, O. Kilgus, U. Luthi, T. Luger, and L. Bruckner-Tuderman Some, but Not All, Glycine Substitution Mutations in COL7A1 Result in Intracellular Accumulation of Collagen VII, Loss of Anchoring Fibrils, and Skin Blistering J. Biol. Chem., July 24, 1998; 273(30): 19228 - 19234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-C. Yu, Y.-C. Twu, C.-Y. Chang, and M. Lin Molecular Basis of the Kell-null Phenotype. A MUTATION AT THE SPLICE SITE OF HUMAN KEL GENE ABOLISHES THE EXPRESSION OF KELL BLOOD GROUP ANTIGENS J. Biol. Chem., March 23, 2001; 276(13): 10247 - 10252. [Abstract] [Full Text] [PDF]
|
|