OMIA:001678-9796 : Epidermolysis bullosa, junctionalis, LAMC2-related in Equus caballus
In other species: sheep , taurine cattle
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 226700 (trait) , 226650 (trait) , 150292 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2002
Cross-species summary: Junctional epidermolysis bullosa, Herlitz-type is a severe subtype of junctional epidermolysis bullosa (JEB) characterized by blisters and extensive erosions, localized to the skin and mucous membranes. [ Orphanet:79404 ]
Species-specific name: Junctional epidermolysis bullosa
Species-specific symbol: JEB
Species-specific description: Several cases of junctional epidermolysis bullosa (JEB) were described for Belgian draft horse foals and similarity to a condition in humans was identified (Frame et al., 1988; Johnson et al. 1988; Kohn et al., 1989; Shapiro and McEwen, 1995). A likely causal variant was identified in the LAMC2 gene (Spirito et al., 2002). The same variant was later reported to cause JEB in the Trait Briton and the Trait Comtois draft horses in France (Milenkovic et al., 2003), and in an Italian draft horse (Cappelli et al., 2015).
[IT thanks Margaret Higgins, working under the guidance of Professor Ernie Bailey, for contributions to this entry in April 2022]
Inheritance: A mare produced two affected foals when bred to two different stallions (Kohn et al., 1989). Similarity to a hereditary condition in people suggested a recessive, autosomal mode of inheritance. Histological studies suggested an absence of the LAMC2 gene product, making this a primary candidate gene for sequencing. After the variant in LAMC2 was identified a pedigree study involving 148 Belgian horses from the United States confirmed the autosomal recessive mode of inheritance (Spirito et al., 2002).
Molecular basis: By cloning and sequencing a very likely candidate gene (based on the disorder being associated with "the absent expression of the gamma2 chain of laminin 5"), Spirito et al. (2002) identified a likely causal mutation as a single bp duplication in the equine LAMC2 gene, namely "1368insC [which] results in a downstream premature termination codon and is predicted to cause absent expression of the laminin gamma2 polypeptide".
The first reports of this disorder in French and later Italian draft horses involved the same mutation (published as 1368insC in LAMC2) as apparently causal (Milenkovic et al., 2003; Cappelli et al., 2015).
Clinical features: "Lesions can be present at birth or develop over a short period of time and are characterized by the development of vesicles and bullae that rapidly progress to erosions and ulcerations at sites of minor trauma such as the lips, the oral mucosa, and distal extremities and the coronary band, with resulting sloughing of the hoofs ... . Lesions can be secondarily affected or become pustules. Affected animals may die soon after birth due to inability to suckle.“ (Capelli et al. 2015)
Pathology: Spirito et al. (2002): "Electron microscopy examination revealed junctional blistering and abnormal hemidesmosomes (Johnson et al., 1988)"
Breeds: Belgian Draft (Horse) (VBO_0000915), Breton, France (Horse) (VBO_0010460), Cavallo Agricolo Italiano da Tiro Pesante Rapido, Italy (Horse) (VBO_0011580), Comtois (Horse) (VBO_0000936).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|LAMC2||laminin, gamma 2||Equus caballus||5||NC_009148.3 (17461884..17513382)||LAMC2||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|599||Belgian Draft (Horse) Breton, France (Horse) Cavallo Agricolo Italiano da Tiro Pesante Rapido, Italy (Horse) Comtois (Horse)||Epidermolysis bullosa, junctionalis, LAMC2-related||LAMC2||insertion, small (<=20)||Naturally occurring variant||EquCab3.0||5||g.17498175dup||c.1372dup||p.(R458Pfs)||NM_001081768.1; NP_001075237.1; published as c.1368insC; coordinates in the table have been updated to HGVS nomenclature (3'-rule) and recent reference genome and / or transcript inforamtion 1,372 Protein position: 458||2002||12230513||The genomic position in EquCab3.0 was provided by Margaret Higgins, working under the guidance of Professor Ernie Bailey [April 2022]|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2015||Cappelli, K., Brachelente, C., Passamonti, F., Flati, A., Silvestrelli, M., Capomaccio, S. :|
|First report of junctional epidermolysis bullosa (JEB) in the Italian draft horse. BMC Vet Res 11:55, 2015. Pubmed reference: 25889423 . DOI: 10.1186/s12917-015-0374-0.|
|2003||Baird ,J.D., Millon, L.V., Dileanis, S., Penedo, M.C.T., Charlesworth, A., Spirito, F., Meneguzzi, G. :|
|Junctional epidermolysis bullosa in Belgian draft horses. Proc Am Assoc Equine Practnr 49:122-126, 2003.|
|Milenkovic, D., Chaffaux, S., Taourit, S., Guerin, G. :|
|A mutation in the LAMC2 gene causes the Herlitz junctional epidermolysis bullosa (H-JEB) in two French draft horse breeds Genetics Selection Evolution 35:249-56, 2003. Pubmed reference: 12633536 . DOI: 10.1051/gse:2003007.|
|2002||Spirito, F., Charlesworth, A., Linder, K., Ortonne, JP., Baird, J., Meneguzzi, G. :|
|Animal models for skin blistering conditions: absence of laminin 5 causes hereditary junctional mechanobullous disease in the Belgian horse. J Invest Dermatol 119:684-91, 2002. Pubmed reference: 12230513 . DOI: 10.1046/j.1523-1747.2002.01852.x.|
|1995||Shapiro, J., McEwen, B. :|
|Mechanobullous disease in a Belgian foal in eastern Ontario. Canadian Veterinary Journal 36:572, 1995.|
|1989||Kohn, C.W., Johnson, G.C., Garry, F., Johnson, C.W., Martin, S., Scott, D.W. :|
|Mechanobullous disease in two Belgian foals Equine Veterinary Journal 21:297-301, 1989. Pubmed reference: 2767032 .|
|1988||Frame, S.R., Harrington, D.D., Fessler, J., Frame, P.F. :|
|Hereditary junctional mechanobullous disease in a foal Journal of the American Veterinary Medical Association 193:1420-1424, 1988. Pubmed reference: 3209456 .|
|Johnson, G.C., Kohn, C.W., Johnson, C.W., Garry, F., Scott, D., Martin, S. :|
|Ultrastructure of junctional epidermolysis bullosa in Belgian foals. J Comp Pathol 99:329-36, 1988. Pubmed reference: 3204167 . DOI: 10.1016/0021-9975(88)90053-9.|
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