Categories: Mortality / aging (incl. embryonic lethal)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609078 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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."

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 [114] Marchigiana bulls was <2%."

Breeds: Marchigiana (Cattle) (VBO_0000291), Romagnola (Cattle) (VBO_0000360).
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: