OMIA 002560-9913 : Growth and respiratory lethal syndrome in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 131241 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2022

Species-specific symbol: GRL syndrome

History: Eusebi et al. (2022) provided the first report of this syndrome.

Inheritance: Eusebi et al. (2022) conducted a detailed pedigree analysis which suggested an "hypothesis of a variant that severely affects the function of a major gene following a classic Mendelian recessive mode of inheritance".

Mapping: Eusebi et al. (2022) "performed a genome-wide association study on a cohort of 13 affected calves and 24 putative non-carrier parents, mapping the disease to a wide 6 cM region on bovine chromosome 3 (p< 10−7)."

Molecular basis: Eusebi et al. (2022): "Whole genome resequencing of three affected calves and three putative non-carrier parents identified a novel missense variant (c.149G>A|p.Cys50Tyr) in exon 2 of the endothelin 2 (EDN2) gene. Bioinformatic analyses of p.Cys50Tyr effects predicted them to be damaging for both the structure and the function of the edn2 protein, and to create a new site of splicing that may also affect the pattern of pre-mRNA splicing and exon definition. Sanger sequencing of this variant on the rest of the sample set confirmed the segregation pattern obtained with whole genome re-sequencing".

Clinical features: Eusebi et al. (2022): "The first five affected calves appeared in 2004 in a Lidia herd and were reported to be suffering from a novel bovine syndrome exhibiting severe growth retardation, respiratory alterations and juvenile lethality. Various systems were affected, including muscular, skeletal and respiratory abnormalities. At the muscular level, the calves displayed weakness, muscular atrophy, impaired mobility and prostration. Skeletal alterations include arched posture and convex frontonasal profile . . . . The respiratory tract was affected by malformation of the nasal turbinate, which may be the cause of the notorious snoring described in these calves, and trachea, with a progressive reduction of the endotracheal lumen . . . and the fusion of tracheal cartilage rings . . . . Finally, feeding difficulties and dehydration were also reported in these calves, probably as a consequence of the abnormalities previously described. This GRL syndrome can be diagnosed at birth in most cases, and all affected calves died before 1 year of age."

Breed: Lidia.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
EDN2 endothelin 2 Bos taurus 3 NC_037330.1 (104679329..104706954) EDN2 Homologene, Ensembl, NCBI gene

Variants

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.

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
1474 Lidia Growth and respiratory lethal syndrome EDN2 missense Naturally occurring variant ARS-UCD1.2 3 g.104701617G>A c.149G>A p.(C50Y) ENSBTAG00000021434; ENSBTAT00000028571.3 2022 35912509

Reference


2022 Eusebi, P.G., Cortés, Ó., Contreras, E., Cañón, J., Dunner, S., Sevane, N. :
A novel missense variant in endothelin-2 (EDN2) causes a growth and respiratory lethal syndrome in bovine. Anim Genet 53:583-591, 2022. Pubmed reference: 35912509. DOI: 10.1111/age.13246.

Edit History


  • Created by Frank Nicholas on 12 Aug 2022
  • Changed by Frank Nicholas on 12 Aug 2022