OMIA:001935-9913 : Zinc deficiency-like syndrome in Bos taurus (taurine cattle)
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 618488 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2014
Species-specific description: Jung et al. (2014) were very careful to note that "Although the phenotype of affected calves strongly resembles BHZD [bovine hereditary zinc deficiency], a zinc deficiency resulting from malabsorption is unlikely to be responsible for the diseased Fleckvieh calves."
Mapping: Having excluded (by sequencing) the SLC39A4 gene, mutations in which cause hereditary zinc deficiency in Holstein-Friesians (see OMIA 000593-9913), Jun et al. (2014) conducted a GWAS on 8 affected calves and 1,339 normal Fleckvieh bulls (each of which had been genotyped with the Illumina BovineHD BeadChip (yielding 644,450 informative SNPs), which mapped this disorder to chromosome BTA21, in "an 18.19 Mb interval from 53,140,245 bp to 71,333,740 bp". Subsequent "Autozygosity mapping within the distal region of BTA 21 revealed a common 1,023 kb segment of extended homozygosity in the eight affected animals (70,550,045 bp – 71,573,501 bp)".
Molecular basis: Analysis of whole-genome sequence data in the candidate region (see Mapping section above), from one affected calf and 42 normal Fleckviehs enabled Jung et al. (2014) "revealed a nonsense mutation (p.W215X) in a phospholipase encoding gene (PLD4) as candidate causal polymorphism". The causality of this mutation was confirmed by sequencing for this mutation in "3,650 animals representing three different breeds". The complete description of the mutation is "c.G645A, p.W215X, BTA 21:71,001,232 bp, rs378824791".
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: As reported by Jun et al. (2014), "Seven calves between the age of seven and 17 weeks with severe skin lesions and poor general health status were admitted to the Clinic of Ruminants. Clinical findings such as scaling and crusting of skin and secondary adhesion of hair were most evident around the muzzle, the eyes, above the sternum and on the extremities . . . . Skin of the inguinal region was seborrhoeic and all palpable lymph nodes were enlarged. The calves suffered from erosions in the interdigital spaces and erosive or ulcerative lesions of the oral mucosa . . . . All animals were underdeveloped in height and weight and had a history of recurring diarrhoea and pneumonia. Two of the calves were supplemented with dietary zinc (750 mg/day), but did not respond to the treatment. Due to the advanced state of the disease and with no prospect for improvement, all animals were euthanized and subjected to necropsy. In hematoxylin and eosin (H&E) stained sections, the skin of the affected animals displayed a mild to severe chronic dermatitis with serocellular crusting and partial superficial bacterial colonization. Multiple intracorneal and intraepidermal accumulations of serum as well as multiple ulcerations and epidermal necroses were present. The epidermis was severely oedematous in multiple sections . . . . Dermis and epidermis were diffusely infiltrated by a moderate to high number of neutrophils. Besides moderate oedema, the dermis exhibited infiltration with lymphocytes and plasma cells to a limited extent. In the cases where the thymus was examined, decreased thymic cellularity and poorly demarcated cortex-medulla-border were observed. Further, the clinical diagnoses of enteritis and pneumonia were confirmed during the pathological examination."
Simmental (Cattle) (VBO_0000380).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|PLD4||phospholipase D family member 4||Bos taurus||21||NC_037348.1 (69348995..69356043)||PLD4||Homologene, Ensembl , NCBI gene|
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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|
|339||Simmental (Cattle)||Zinc deficiency-like syndrome||PLD4||nonsense (stop-gain)||Naturally occurring variant||ARS-UCD1.2||21||g.69352995G>A||c.702G>A||p.(W234*)||UMD3.1 position is g.71001232G>A||rs378824791||rs378824791||2014||25052073||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; rsID gleaned from or confirmed by Table 1 of Â Sharma et al. (2017) Animal Genetics 48(3):369-370. The genomic location on ARS-UCD1.2 was determined by Katie Eager and Shernae Woolley, EMAI, NSW. Department of Primary Industries.|
Cite this entry
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.
|2022||Langenmayer, M.C., Jung, S., Fux, R., Wittlinger, C., Tschoner, T., Majzoub-Altweck, M., Knubben-Schweizer, G., Fries, R., Hermanns, W., Trefz, F.M. :|
|Macrophages in dermal disease progression of phospholipase D4-deficient Fleckvieh calves. Vet Pathol 59:319-327, 2022. Pubmed reference: 34856834. DOI: 10.1177/03009858211062629.|
|2018||Langenmayer, M.C., Jung, S., Majzoub-Altweck, M., Trefz, F.M., Seifert, C., Knubben-Schweizer, G., Fries, R., Hermanns, W., Gollnick, N.S. :|
|Zinc deficiency-like syndrome in Fleckvieh calves: Clinical and pathological findings and differentiation from bovine hereditary zinc deficiency. J Vet Intern Med 32:853-859, 2018. Pubmed reference: 29424482. DOI: 10.1111/jvim.15040.|
|2014||Jung, S., Pausch, H., Langenmayer, M.C., Schwarzenbacher, H., Majzoub-Altweck, M., Gollnick, N.S., Fries, R. :|
|A nonsense mutation in PLD4 is associated with a zinc deficiency-like syndrome in Fleckvieh cattle. BMC Genomics 15:623, 2014. Pubmed reference: 25052073. DOI: 10.1186/1471-2164-15-623.|
- Created by Frank Nicholas on 25 Oct 2014
- Changed by Frank Nicholas on 25 Oct 2014
- Changed by Frank Nicholas on 29 Oct 2014