OMIA 001677-9615 : Epidermolysis bullosa, junctionalis, LAMA3-related in Canis lupus familiaris

In other species: horse , cattle

Category: Integument (skin) phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 226700 (trait) , 600805 (gene) , 245660 (trait) , 226650 (trait)

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: 2005

Cross-species summary: Congenital blistering skin disease characterized by separation of the lamina lucida of the basement membrane zone. Blisters often occur in and around the mouth and on the limbs, leading in the latter case to separation of the hoof or nail from the corium (dermis).

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Capt et al. (2005) were able to report that "The condition is associated with reduced expression of laminin 5 caused by a homozygous insertion (4818+207ins6.5 kb) of repetitive satellite DNA within intron 35 of the gene (LAMA3) for the laminin alpha3 chain. The intronic mutation interferes with maturation of the alpha3 pre-messenger RNA resulting in the coexpression of a transcript with a 227 nucleotide insertion and a wild-type mRNA that encodes scant amounts of the alpha3 polypeptide."

Herrmann et al. (2021): “Whole genome sequencing (WGS) of one affected [Australian cattle dog cross-bred] puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. … The WGS revealed a novel missense variant in the laminin α3-chain XP_537297.2p(Asp2867Val). … Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant.”

Clinical features: Herrmann et al. (2021): "Five of eight puppies in an Australian cattle dog cross-bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress."

Pathology: Herrmann et al. (2021): “Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post-mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway.”

Breeds: Australian Cattle Dog X, German Pointer.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
LAMA3 laminin, alpha 3 Canis lupus familiaris 7 NC_051811.1 (64714403..64463775) LAMA3 Homologene, Ensembl, NCBI gene

Variants

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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
701 German Pointer Epidermolysis bullosa, junctionalis, LAMA3 LAMA3 insertion, gross (>20) Naturally occurring variant 7 "insertion (4818+207ins6.5 kb) of repetitive satellite DNA within intron 35 of the gene (LAMA3)" 2005 15737193
1324 Australian Cattle Dog X Epidermolysis bullosa, junctionalis, LAMA3 LAMA3 missense Naturally occurring variant CanFam3.1 7 g.64427161T>A c.8615T>A p.(D2867V) cDNA and protein positions based on XM_537297.6 and XP_537297.2, respectively 2021 34250689

References


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. > > > > > >
2021 Frattini, S., Polli, M., Cortellari, M., Negro, A., Bionda, A., Riva, J., Rizzi, R., Marelli, S., Crepaldi, P. :
Genetic trend of the junctional epidermolysis bullosa in the German shorthaired pointer in Italy. Vet Rec Open 8:e15, 2021. Pubmed reference: 34457315. DOI: 10.1002/vro2.15.
Herrmann, I., Linder, K.E., Meurs, K.M., Friedenberg, S.G., Cullen, J., Olby, N., Bizikova, P. :
Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement. Vet Dermatol 32:379-e108, 2021. Pubmed reference: 34250689. DOI: 10.1111/vde.12972.
2005 Capt, A., Spirito, F., Guaguere, E., Spadafora, A., Ortonne, J.P., Meneguzzi, G. :
Inherited junctional epidermolysis bullosa in the German Pointer: establishment of a large animal model. J Invest Dermatol 124:530-5, 2005. Pubmed reference: 15737193. DOI: 10.1111/j.0022-202X.2004.23584.x.
2003 Guaguere, E., Capt, A., Spirito, F., Meneguzzi, G. :
Junctional epidermolysis bullosa in the german shorthaired pointer: a spontaneous model for junctional epidermolysis bullosa in man Bull Acad Vet France 157:47-51, 2003.
1997 Nagata, M., Iwasaki, T., Masuda, H., Shimizu, H. :
Non-lethal junctional epidermolysis bullosa in a dog British Journal of Dermatology 137:445-449, 1997. Pubmed reference: 9349347.
Olivry, T., Poujadedelverdier, A., Dunston, S.M., Fine, J.D., Ortonne, J.P. :
Absent expression of collagen xvii (BPAG2, BP180) in canine familial localized junctional epidermolysis bullosa Veterinary Dermatology 8:203-212, 1997. Pubmed reference: 34644840.

Edit History


  • Created by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 21 Oct 2012
  • Changed by Imke Tammen2 on 06 Aug 2021
  • Changed by Imke Tammen2 on 02 Sep 2021