In contrast, biallelic loss-of-function variants in LAMB3 cause recessive junctional epidermolysis bullosa, characterized by life-threatening skin fragility.
Herein, we report the first application of CRISPR/Cas9-mediated homology direct repair (HDR) to in situ restore LAMB3 expression in JEB keratinocytes in vitro and in immunodeficient mice transplanted with genetically corrected skin equivalents.
Recessive mutations in the LAMA3, LAMB3 and LAMC2 genes that encode laminin-332 (LM332) (α3a, β3 and γ2 chains, respectively) cause different junctional epidermolysis bullosa (JEB) subtypes.
Targeted next-generation sequencing identifies a novel mutation of LAMB3 in a Chinese neonatal patient presented with junctional epidermolysis bullosa.
When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB), while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility.
A subgroup, coined JEB-other, is associated with mutations in the COL17A1 gene encoding collagen XVII or, more rarely, with mutations in the laminin 332 genes LAMA3, LAMB3, or LAMC2.
Epidermal stem cells from an adult patient affected by LAM5-beta3-deficient JEB were transduced with a retroviral vector expressing LAMB3 cDNA (encoding LAM5-beta3), and used to prepare genetically corrected cultured epidermal grafts.
Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes for an infant with Herlitz junctional epidermolysis bullosa.
These results indicate that the Herlitz JEB phenotype in this patient is due to complete paternal isodisomy of chromosome 1 and reduction to homozygosity of the mutant LAMB3 gene locus.
Markedly reduced staining for laminin 5 indicated the Herlitz type of JEB (OMIM 226700), which could be confirmed by mutation analysis in the LAMB3 gene, showing homozygous nonsense mutations.
This report documents compound heterozygosity for novel mutations in LAMB3 of a Japanese patient showing typical clinical features of generalized atrophic benign epidermolysis bullosa.
In this study, we examined the LAMB3 gene for mutations in 22 Herlitz junctional epidermolysis bullosa families, and identified 15 distinct mutations, eight of them previously unreported, bringing the total number of distinct Herlitz junctional epidermolysis bullosa mutations in LAMB3 to 35.
Mutations in the genes (LAMA3, LAMB3, and LAMC2) encoding the subunit polypeptides of the cutaneous basement membrane zone protein laminin 5 have been reported in different forms of junctional epidermolysis bullosa (JEB), an inherited blistering skin disease.
In this study, we performed genetic analyses in two unrelated Japanese families with Herlitz junctional epidermolysis bullosa and identified two novel nonsense mutations in the LAMB3 gene.