OMIA:001722-9913 : Lethal multi-organ developmental dysplasia in Bos taurus (taurine cattle)
Categories: Mortality / aging (incl. embryonic lethal)
Possibly relevant human trait(s) and/or gene(s) (MIM number): 609078 (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: 2012
Species-specific name: Paunch calf syndrome
History: This disorder was first reported by Testoni et al. (2009).
Mapping: Testoni et al. (2012) "localized the causative mutation to a 1.2 Mb interval on BTA 17 by genome-wide association and identical by descent mapping".
Molecular basis: Using targeted DNA capture and massively parallel resequencing of the 1.2 Mb region that contained 24 genes, Testoni et al. (2012) identified a causal mutation as a "KDM2B missense mutation (c.2503G>A) leading to an amino acid exchange (p.D835N) in an evolutionary strongly conserved domain". As the same authors report, "The KDM2B gene (also known as JHDM1B and FBXL10) encodes a histone H3 lysine 36 dimethyl (H3K36me2)-specific demethylase . . . Histone methylation is one important transcription regulatory system that affects mammalian development and cell differentiation".
Murgiano et al. (2020) reported the same variant as being causal in an affected Marchigiana male still-born calf: "The affected animal was the offspring of consanguineous mating and homozygous presence of the KDM2B missense variant was confirmed. Both parents were heterozygous for [the] KDM2B [variant]". Also, as the authors noted, "it cannot be excluded that the variant already was present before the Marchigiana breed was established as distinct breed, and therefore it may represent the identical variant as in the Romagnola breed."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: As summarised by Testoni et al. (2012), this disorder is "mainly characterized by facial deformities, ascites and hepatic fibrosis"
Prevalence: Murgiano et al. (2014) reported that the "prevalence of carriers within top-ranked Romagnola sires over the years 2007-2012 was 29.3% (allele frequency 14.6%). In young bull calves, 30.9% were carriers with an allele frequency of 15.4%."
Murgiano et al. (2020) reported "the prevalence of carriers in a selected population of  Marchigiana bulls was <2%."
Marchigiana (Cattle) (VBO_0000291),
Romagnola (Cattle) (VBO_0000360).
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|
|KDM2B||lysine (K)-specific demethylase 2B||Bos taurus||17||NC_037344.1 (53650993..53769702)||KDM2B||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|
|196||Marchigiana (Cattle) Romagnola (Cattle)||Lethal multi-organ developmental dysplasia||KDM2B||missense||Naturally occurring variant||ARS-UCD1.2||17||g.53761149G>A||c.2503G>A||p.(D835N)||2012||23029151||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)|
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||Jacinto, J.G.P., Sbarra, F., Quaglia, A., Gentile, A., Drögemüller, C. :|
|Short communication: Prevalence of deleterious variants causing recessive disorders in Italian Chianina, Marchigiana and Romagnola cattle. Animal 16:100569, 2022. Pubmed reference: 35717834. DOI: 10.1016/j.animal.2022.100569.|
|2020||Murgiano, L., Militerno, G., Sbarra, F., Drögemüller, C., G P Jacinto, J., Gentile, A., Bolcato, M. :|
|KDM2B-associated paunch calf syndrome in Marchigiana cattle. J Vet Intern Med , 2020. Pubmed reference: 32515858. DOI: 10.1111/jvim.15789.|
|2014||Murgiano, L., Drögemüller, C., Sbarra, F., Bolcato, M., Gentile, A. :|
|Prevalence of paunch calf syndrome carriers in Italian Romagnola cattle. Vet J 200:459-61, 2014. Pubmed reference: 24792452. DOI: 10.1016/j.tvjl.2014.03.020.|
|2012||Testoni, S., Bartolone, E., Rossi, M., Patrignani, A., Bruggmann, R., Lichtner, P., Tetens, J., Gentile, A., Drögemüller, C. :|
|KDM2B is implicated in bovine lethal multi-organic developmental dysplasia. PLoS One 7:e45634, 2012. Pubmed reference: 23029151. DOI: 10.1371/journal.pone.0045634.|
|2009||Testoni, S., Militerno, G., Rossi, M., Gentile, A. :|
|Congenital facial deformities, ascites and hepatic fibrosis in Romagnola calves. Vet Rec 164:693-4, 2009. Pubmed reference: 19483213.|
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