In other species: sheep

Categories: Homeostasis / metabolism phene , Immune system 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

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: See also entries for Hydrops foetalis: OMIA:000493

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: