OMIA:001562-9913 : Pulmonary hypoplasia with anasarca in Bos taurus (taurine cattle)

Categories: Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 618154 (trait) , 605011 (gene)

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; PMID 32069517): "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." Häfliger et al. (2020; PMID 33006153) reported an aborted Holstein foetus affected with PHA, for which whole-genome sequencing revealed no likely causal variant, but for which comparison of "read depth of 500 kb windows across" the genome revealed an extra chromosome 20, i.e. trisomy 20

Molecular basis: Häfliger et al. (2020; PMID 32069517): "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; PMID 32069517): "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; PMID 32069517) 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 (Cattle) (VBO_0000142), Cikasto govedo, Slovenia (Cattle) (VBO_0005270), Danish Holstein (Cattle) (VBO_0000190), Dexter (Cattle) (VBO_0000193), Hereford (Cattle) (VBO_0000232), Maine-Anjou (Cattle) (VBO_0000286), Shorthorn (Cattle) (VBO_0000375).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

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


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 Year Published PubMed ID(s) Acknowledgements
1163 Cikasto govedo, Slovenia (Cattle) Pulmonary hypoplasia and anasarca syndrome ADAMTS3 missense Naturally occurring variant ARS-UCD1.2 6 g.87462016G>A c.1222C>T p.(H408T) NM_001192797.1: c.1222C>T; NP_001179726.1: p.(His408Tyr) (Häfliger et al., 2020) rs5334475098 2020 32069517

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2020). OMIA:001562-9913: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2024 Mee, J.F., Murphy, D., Curran, M. :
Bovine congenital defects recorded by veterinary practitioners. Reprod Domest Anim 59:e14501, 2024. Pubmed reference: 37975255. DOI: 10.1111/rda.14501.
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 51:382-390, 2020. Pubmed reference: 32069517. DOI: 10.1111/age.12923.
Häfliger, I.M., Agerholm, J.S., Drögemüller, C. :
Constitutional trisomy 20 in an aborted Holstein fetus with pulmonary hypoplasia and anasarca syndrome. Anim Genet 51:988-989, 2020. Pubmed reference: 33006153. DOI: 10.1111/age.13008.
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
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