Compound heterozygosity for an out-of-frame deletion and a splice site mutation in the LAMB3 gene causes nonlethal junctional epidermolysis bullosa

P Posteraro, S Sorvillo, L Gagnoux-Palacios… - Biochemical and …, 1998 - Elsevier
P Posteraro, S Sorvillo, L Gagnoux-Palacios, C Angelo, M Paradisi, G Meneguzzi…
Biochemical and biophysical research communications, 1998Elsevier
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 …
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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