Alternative titles; symbols
ORPHA: 79402;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q25.3 | Epidermolysis bullosa, junctional 3A, intermediate | 619785 | Autosomal recessive | 3 | LAMC2 | 150292 |
A number sign (#) is used with this entry because of evidence that intermediate junctional epidermolysis bullosa 3A (JEB3A) is caused by compound heterozygous or homozygous mutation in the LAMC2 gene (150292) on chromosome 1q25.
Intermediate junctional epidermolysis bullosa 3A (JEB3A) is an autosomal recessive blistering disease of skin and mucous membranes. Blistering is less severe than in severe JEB (see 226700). The plane of skin cleavage is through the lamina lucida of the cutaneous basement membrane zone. Nail and dental abnormalities occur. Blistering does not affect the life span of affected individuals (summary by Has et al., 2020).
For a discussion of genetic heterogeneity of the subtypes of JEB, see JEB1A (226650).
Reviews
Has et al. (2020) reviewed the clinical and genetic aspects, genotype-phenotype correlations, disease-modifying factors, and natural history of epidermolysis bullosa.
Nakano et al. (2002) studied a 7-year-old Turkish girl (patient 25) with non-Herlitz JEB and mutation in the LAMC2 gene. She had generalized moderate blisters with nail and dental abnormalities. Electron microscopy revealed hypoplastic hemidesmosomes. Immunofluorescence studies showed reduced laminin-5 staining. The patient was identified in a cohort of 27 probands with JEB, 12 with the non-Herlitz subtype, and mutations in one of the laminin-5 subunit genes.
Castiglia et al. (2001) described a 7-year-old boy, the first child of healthy nonconsanguineous parents, with non-Herlitz JEB and mutation in the LAMC2 gene. Generalized trauma-induced skin blisters and erosions had been present since birth, as well as nail and tooth abnormalities. Mucosal lesions were limited to transient blisters of the nasal cavity. Ultrastructural examination of a skin biopsy demonstrated that the plane of cleavage lay within the lamina lucida of the dermal-epidermal junction. Hemidesmosomes were hypoplastic.
The transmission pattern of JEB3A in the family reported by Castiglia et al. (2001) was consistent with autosomal recessive inheritance.
In a 7-year-old Turkish girl (patient 25) with non-Herlitz JEB, Nakano et al. (2002) identified a homozygous mutation in the LAMC2 gene (R245X; 150292.0006). Functional studies in keratinocytes from the patient showed that the mutation resulted in alternative splicing patterns that removed the mutation-bearing exon while maintaining the reading frame.
In a 7-year-old boy with non-Herlitz JEB, Castiglia et al. (2001) detected compound heterozygosity for mutations in the LAMC2 gene: a splice site mutation in intron 3, c.522-1G-A (150292.0007), and a single-base insertion in exon 23, c.3511insA (150292.0008). The insertion was inherited from the mother, and the splice site mutation occurred as a de novo event on the paternal allele. The c.522-1G-A mutation resulted in in-frame skipping of exon 4 and synthesis of a mutated gamma-2 polypeptide (gamma-2-delta-4) carrying a 33-amino acid deletion within the N-terminal domain V. Transfection of this mutant cDNA into LAMC2-null keratinocytes resulted in restoration of laminin-5 deposition onto the culture substrate. The c.3511insA mutation did not result in laminin-5 secretion and extracellular processing.
Castiglia, D., Posteraro, P., Spirito, F., Pinola, M., Angelo, C., Puddu, P., Meneguzzi, G., Zambruno, G. Novel mutations in the LAMC2 gene in non-Herlitz junctional epidermolysis bullosa: effects on laminin-5 assembly, secretion, and deposition. J. Invest. Derm. 117: 731-739, 2001. [PubMed: 11564184] [Full Text: https://doi.org/10.1046/j.0022-202x.2001.01453.x]
Has, C., Bauer, J. W., Bodemer, C., Bolling, M. C., Bruckner-Tuderman, L., Diem, A., Fine, J. D., Heagerty, A., Hovnanian, A., Marinkovich, M. P., Martinez, A. E., McGrath, J. A., and 10 others. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Brit. J. Derm. 183: 614-627, 2020. [PubMed: 32017015] [Full Text: https://doi.org/10.1111/bjd.18921]
Nakano, A., Chao, S.-C., Pulkkinen, L., Murrell, D., Bruckner-Tuderman, L., Pfendner, E., Uitto, J. Laminin 5 mutations in junctional epidermolysis bullosa: molecular basis of Herlitz vs non-Herlitz phenotypes. Hum. Genet. 110: 41-51, 2002. [PubMed: 11810295] [Full Text: https://doi.org/10.1007/s00439-001-0630-1]