Alternative titles; symbols
ORPHA: 79402;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 18q11.2 | Epidermolysis bullosa, junctional 2A, intermediate | 619783 | Autosomal recessive | 3 | LAMA3 | 600805 |
A number sign (#) is used with this entry because of evidence that intermediate junctional epidermolysis bullosa 2A (JEB2A) is caused by homozygous or compound heterozygous mutation in the LAMA3 gene (600805) on chromosome 18q11.
Intermediate junctional epidermolysis bullosa 2A (JEB2A) 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. Oral mucosa may be involved and nail bed blistering has been reported. 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) identified 2 patients with non-Herlitz JEB and mutations in the LAMA3 gene, a 15-month-old Saudi Arabian girl (patient 26) and a 33-month-old Caucasian boy (patient 27). The girl was reported to have blisters on the trunk and extremities. Electron microscopy demonstrated skin cleavage above the basal lamina and below the basal cells. The boy had blisters on the face, oral mucosa, and nail beds, and no scarring or milia. Electron microscopy indicated normal hemidesmosomes. Immunofluorescence studies showed normal laminin-5 staining. The individuals were 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.
The transmission pattern of JEB2A in the families reported by Nakano et al. (2002) was consistent with autosomal recessive inheritance.
In a 15-month-old Saudi Arabian girl (patient 26) with non-Herlitz JEB, Nakano et al. (2002) identified a homozygous mutation in the LAMA3 gene (Q1368X; 600805.0003). The authors also identified compound heterozygosity for a missense (R1331C; 600805.0005) and a splice site mutation (600805.0006) in a 33-month-old Caucasian boy (patient 27).
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]