Alternative titles; symbols
ORPHA: 79404;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q25.3 | Epidermolysis bullosa, junctional 3B, severe | 619786 | Autosomal recessive | 3 | LAMC2 | 150292 |
A number sign (#) is used with this entry because of evidence that severe junctional epidermolysis bullosa 3B (JEB3B) is caused by homozygous mutations in the LAMC2 gene (150292) on chromosome 1q25.
Severe junctional epidermolysis bullosa 3B (JEB3B) is an autosomal recessive skin blistering disorder characterized by extreme fragility of the skin and epithelia of various extracutaneous tissues. Skin blisters and erosions are present at birth. The plane of skin cleavage is through the lamina lucida of the cutaneous basement membrane zone. Patients die in infancy to early adulthood (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.
Aberdam et al. (1994) studied 8 southern Italian and French families in which the diagnosis of JEB Herlitz type was based on clinical observation of extensive blistering and erosions with crusting and thickened granulation tissue noted shortly after birth. Electron microscopy demonstrated that blisters were within the lamina lucida of the dermoepidermal basement membrane, with epidermis at the roof and lamina densa at the base both intact. Intact patient skin samples failed to stain with GB3 and 19-DEJ-1 monoclonal antibodies. In 4 of these families, linkage to the LAMC2 gene was demonstrated.
Pulkkinen et al. (1994) described a Hispanic woman (JEB1) with JEB Herlitz type and mutation in the LAMC2 gene. She had multiple erosions and hemorrhagic blisters. She had lost nails on fingers and toes; there was no evidence of digit fusion. She died at age 23 years. A similarly affected older sister had died at age 21 years. Parents and 1 sib were unaffected.
Takizawa et al. (2000) reported a 2-month-old Japanese girl with JEB Herlitz type. Blistering of skin and oral mucous membranes was noted at birth. Immunofluorescence analysis of skin revealed negative laminin-5 staining but positive collagen VII staining. The child died at age 8 months.
Nakano et al. (2002) reported a male infant (patient 10) with JEB Herlitz type and mutation in the LAMC2 gene. Generalized blisters, abnormal nails, and skin cleavage at the level of the lamina lucida were reported. He died at 4 months of age. The individual was identified in a cohort of 27 probands with JEB, 15 with the Herlitz subtype, and mutations in one of the laminin-5 subunit genes.
The transmission pattern of JEB3B in the family of patient JEB1 reported by Pulkkinen et al. (1994) was consistent with autosomal recessive inheritance.
In a patient (JEB1) with Herlitz junctional epidermolysis bullosa, Pulkkinen et al. (1994) identified a homozygous splice site mutation in the LAMC2 gene (150292.0001).
In affected members of a family (L) with Herlitz junctional epidermolysis bullosa, Aberdam et al. (1994) identified a homozygous arg95-to-ter substitution (R95X; 150292.0002) in exon 3 of the LAMC2 gene.
In affected members of a family with the Herlitz type of junctional epidermolysis bullosa, Baudoin et al. (1994) observed a homozygous nonsense mutation in the LAMC2 gene (Y355X; 150292.0003).
In a Japanese infant with Herlitz junctional epidermolysis bullosa, Takizawa et al. (2000) identified a homozygous cys553-to-ter (C553X; 150292.0004) mutation in the LAMC2 gene. The father was a heterozygous carrier of this mutation, whereas the mother had 2 normal LAMC2 alleles. The patient showed homozygosity for 15 known intragenic polymorphisms in the LAMC2 gene and 16 microsatellite markers spanning the entire chromosome 1 which, when informative, were paternal in origin. Homozygosity resulted from nondisjunction and uniparental disomy involving monosomy rescue.
In a Caucasian male with Herlitz JEB (patient 10) who died at the age of 4 months with generalized blistering and abnormal nails, Nakano et al. (2002) found homozygosity for a 7-bp deletion in the LAMC2 gene (150292.0005).
Aberdam, D., Galliano, M.-F., Vailly, J., Pulkkinen, L., Bonifas, J., Christiano, A. M., Tryggvason, K., Uitto, J., Epstein, E. H., Jr., Ortonne, J.-P., Meneguzzi, G. Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma-2 subunit of nicein/kalinin (laminin-5). Nature Genet. 6: 299-304, 1994. [PubMed: 8012394] [Full Text: https://doi.org/10.1038/ng0394-299]
Baudoin, C., Miquel, C., Gagnoux-Palacios, L., Pulkkinen, L., Christiano, A. M., Uitto, J., Tadini, G., Ortonne, J.-P., Meneguzzi, G. A novel homozygous nonsense mutation in the LAMC2 gene in patients with the Herlitz junctional epidermolysis bullosa. Hum. Molec. Genet. 3: 1909-1910, 1994. [PubMed: 7849725] [Full Text: https://doi.org/10.1093/hmg/3.10.1909]
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]
Pulkkinen, L., Christiano, A. M., Airenne, T., Haakana, H., Tryggvason, K., Uitto, J. Mutations in the gamma-2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa. Nature Genet. 6: 293-298, 1994. [PubMed: 8012393] [Full Text: https://doi.org/10.1038/ng0394-293]
Takizawa, Y., Pulkkinen, L., Chao, S.-C., Nakajima, H., Nakano, Y., Shimizu, H., Uitto, J. Mutation report: complete paternal uniparental isodisomy of chromosome 1: a novel mechanism for Herlitz junctional epidermolysis bullosa. J. Invest. Derm. 115: 307-311, 2000. [PubMed: 10951251] [Full Text: https://doi.org/10.1046/j.1523-1747.2000.00052.x]