OMIA 001948-9940 : Epidermolysis bullosa, junctionalis, ITGB4-related in Ovis aries

In other species: cattle

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 147557 , 226650

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2015

Cross-species summary: Also known as Epidermolysis bullosa, junctional, non-Herlitz type

Mapping: By conducting a GWAS on 20 affected, 28 related normal and 48 unrelated normal Churra sheep, each of which had been genotyped with the Illumina OvineSNP50 BeadChip (yielding 44,785 informative SNPs), Suárez-Vega et al. (2015) mapped this disorder to chromosome OAR11, in the vicinity of marker rs410387229 at 54,939,690 bp (OARv3.1). Subsequent homozygosity mapping narrowed the region to "an 868-kb homozygous segment, from 54,632,309–55,500,100 bp". This implicated a very likely comparative locational candidate gene, namely ITGB4.

Molecular basis: Small deletion in Churra sheep: "a 4-bp deletion within exon 33 of the ITGB4 gene (c.4412_4415del;[ OAR11:54,849,767–54,849,770 bp; Oar v3.1]). The c.4412_4415del mutation causes a frameshift resulting in a premature stop codon at position 1472 of the integrin β4 protein" (Suárez-Vega et al., 2015)

Fabre et al. (2020) conducted whole genome sequencing of 2 unrelated affected French Mouton Vendeen lambs and 1 unaffected fullsib. Analysis of variants identified in 13 candidate genes “identified a novel SNP (OAR11_v4.0, g.54799925G>A) in exon 23 of the ITGB4 gene … whose variant allele causes a premature stop codon (p.Arg885*).” The variant segregated with the junctional epidermolysis bullosa phenotype in six affected lambs, 7 parents and 4 unaffected full-sib lambs (Fabre et al., 2020).

Prevalence: Genotyping for the g.54799925G>A variant in the French Mouton Vendeen meat sheep breed identified estimated allele frequencies of 6.3% in renewal ewe lambs, 5.2% for service rams and 6% in adult ewes (Fabre et al., 2020).

Breeds: Churra, Mouton Vendeen.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ITGB4 integrin beta 4 Ovis aries 11 NC_040262.1 (7395216..7427544) ITGB4 Homologene, Ensembl, NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Churra Epidermolysis bullosa, junctionalis, ITGB4 ITGB4 deletion, small (<=20) Oar_v3.1 11 g.54849767_54849770del c.4412_4415del 2015 25955497
Mouton Vendeen Epidermolysis bullosa, junctionalis, ITGB4 ITGB4 nonsense (stop-gain) Oar_v4.0 11 g.54799925G>A c.2653C>T p.(Arg885*) c.2653C>T position is based on mRNA XM_015098951.1 2020 33225458


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.
2020 Fabre, S., Chantepie, L., Plisson-Petit, F., Sarry, J., Woloszyn, F., Genet, C., Drouilhet, L., Tosser-Klopp, G. :
A novel homozygous nonsense mutation in ITGB4 gene causes epidermolysis bullosa in Mouton Vendéen sheep. Anim Genet :, 2020. Pubmed reference: 33225458. DOI: 10.1111/age.13026.
2015 Suárez-Vega, A., Gutiérrez-Gil, B., Benavides, J., Perez, V., Tosser-Klopp, G., Klopp, C., Keennel, S.J., Arranz, J.J. :
Combining GWAS and RNA-Seq Approaches for Detection of the Causal Mutation for Hereditary Junctional Epidermolysis Bullosa in Sheep. PLoS One 10:e0126416, 2015. Pubmed reference: 25955497. DOI: 10.1371/journal.pone.0126416.

Edit History

  • Created by Frank Nicholas on 17 May 2015
  • Changed by Frank Nicholas on 17 May 2015
  • Changed by Imke Tammen2 on 30 Nov 2020