OMIA 001562-9913 : Pulmonary hypoplasia with anasarca in Bos taurus

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Species-specific symbol: PHA

Mapping: Häfliger et al. (2020): "Under the assumption of monogenic inheritance, genome‐wide homozygosity mapping [Slovenian Cika cattle] scaled down the critical regions to 3% of the bovine genome including a 43.6 Mb‐sized segment on chromosome 6." The same authors reported that "A single PHA case was found in Danish Holstein cattle and was whole‐genome sequenced along with its parents. However, as there was no plausible private protein‐changing variant, mining for structural variation revealed a likely pathogenic trisomy of the entire chromosome 20."

Molecular basis: Häfliger et al. (2020): "Whole‐genome sequencing of one case, variant filtering against controls and genotyping of a larger cohort of Cika cattle led to the detection of a likely pathogenic protein‐changing variant perfectly associated with the disease: a missense variant on chromosome 6 in ADAMTS3 (NM_001192797.1: c.1222C>T), which affects an evolutionary conserved residue (NP_001179726.1: p.(His408Tyr))"

Clinical features: Häfliger et al. (2020): "The affected fetuses show diffuse severe subcutaneous edema, accumulation of fluids in the body cavities (anasarca) and a dysplasia of the lymphatic system in addition to pulmonary hypoplasia or aplasia".

Genetic testing: Since 2006, a DNA test for this disorder in Maine Anjou and some other breeds (developed by Dr Jon Beever, Dept of Animal Sciences, University of Illinois) has been available.

Häfliger et al. (2020) reported that "All three PHA‐affected cases were tested homozygous wt for the variants of the commercial DNA test for bovine PHA", leading them to conclude that "The absence of the unreported but commercially tested variants for bovine PHA indicates that the PHA‐affected calves presented here are unrelated to those that led to the commercial gene test development."

Breeds: Belted Galloway, Danish Holstein, Dexter, Hereford, Maine Anjou, Shorthorn, Slovenian Cika.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif 3 Bos taurus 6 NC_037333.1 (87706149..87425830) ADAMTS3 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.

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
Slovenian Cika Pulmonary hypoplasia and anasarca syndrome ADAMTS3 missense ARS‐UCD1.2 6 g.87,462,016G>A c.1222C>T p.(His408Tyr) NM_001192797.1: c.1222C>T; NP_001179726.1: p.(His408Tyr) (Häfliger et al., 2020) 2020 32069517

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.
2020 Häfliger, I.M., Wiedemar, N., Švara, T., Starič, J., Cociancich, V., Šest, K., Gombač, M., Paller, T., Agerholm, J.S., Drögemüller, C. :
Identification of small and large genomic candidate variants in bovine pulmonary hypoplasia and anasarca syndrome. Anim Genet :, 2020. Pubmed reference: 32069517. DOI: 10.1111/age.12923.
2016 Švara, T., Cociancich, V., Šest, K., Gombač, M., Paller, T., Starič, J., Drögemüller, C. :
Pulmonary hypoplasia and anasarca syndrome in Cika cattle. Acta Vet Scand 58:36, 2016. Pubmed reference: 27267454. DOI: 10.1186/s13028-016-0220-9.
2011 Agerholm, J.S., Arnbjerg, J. :
Pulmonary hypoplasia and anasarca syndrome in a belted Galloway calf Veterinary Record 168:190 only, 2011. Pubmed reference: 21493533. DOI: 10.1136/vr.c6354.
2006 Windsor, PA., Cavanagh, JA., Tammen, I. :
Hydrops fetalis associated with pulmonary hypoplasia in Dexter calves. Aust Vet J 84:278-81, 2006. Pubmed reference: 16911227. DOI: 10.1111/j.1751-0813.2006.00018.x.

Edit History


  • Created by Frank Nicholas on 30 Mar 2011
  • Changed by Frank Nicholas on 24 Nov 2012
  • Changed by Frank Nicholas on 21 Aug 2019
  • Changed by Frank Nicholas on 20 Feb 2020