TY - JOUR
T1 - Compound heterozygosity for an out-of-frame deletion and a splice site mutation in the LAMB3 gene causes nonlethal junctional epidermolysis bullosa
AU - Posteraro, P.
AU - Sorvillo, S.
AU - Gagnoux-Palacios, L.
AU - Angelo, C.
AU - Paradisi, M.
AU - Meneguzzi, G.
AU - Castiglia, D.
AU - Zambruno, G.
PY - 1998/2/24
Y1 - 1998/2/24
N2 - Laminin-5 is the major adhesion ligand of epithelial cells. Mutations in the genes encoding laminin-5 cause junctional epidermolysis bullosa (JEB), a clinically and genetically heterogeneous group of recessively inherited blistering disease of skin and mucous membranes. In this report, we describe a patient with a non-lethal variant of JEB who is a compound heterozygous for mutations affecting the LAMB3 gene. The paternally inherited mutation is a deletion of a single base (T) leading to a frameshift and premature termination codon. It results in mRNA decay. The maternally inherited mutation is a G→A transition at the last base of exon 7 (628G→A) which converts a codon for glutamic acid in a codon for lysine (E210K). The mutation 628G→A alters the correct splicing of LAMB3 pre-mRNA giving rise to two aberrant mRNA, in addition to the RNA transcript carrying the G→A substitution. This result is compatible with the reduced expression of mutated laminin 5 molecules with altered biological activity, and the mild JEB phenotype observed in the patient.
AB - Laminin-5 is the major adhesion ligand of epithelial cells. Mutations in the genes encoding laminin-5 cause junctional epidermolysis bullosa (JEB), a clinically and genetically heterogeneous group of recessively inherited blistering disease of skin and mucous membranes. In this report, we describe a patient with a non-lethal variant of JEB who is a compound heterozygous for mutations affecting the LAMB3 gene. The paternally inherited mutation is a deletion of a single base (T) leading to a frameshift and premature termination codon. It results in mRNA decay. The maternally inherited mutation is a G→A transition at the last base of exon 7 (628G→A) which converts a codon for glutamic acid in a codon for lysine (E210K). The mutation 628G→A alters the correct splicing of LAMB3 pre-mRNA giving rise to two aberrant mRNA, in addition to the RNA transcript carrying the G→A substitution. This result is compatible with the reduced expression of mutated laminin 5 molecules with altered biological activity, and the mild JEB phenotype observed in the patient.
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U2 - 10.1006/bbrc.1998.8180
DO - 10.1006/bbrc.1998.8180
M3 - Article
C2 - 9501007
AN - SCOPUS:0032562076
VL - 243
SP - 758
EP - 764
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -