OMIA:001887-9913 : Osteopetrosis with gingival hamartomas in Bos taurus (taurine cattle)
Categories: Skeleton phene (incl. short stature & teeth)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2014
History: This disorder was first documented by Sartelet et al. (2014).
Inheritance: Sartelet et al. (2014) reported data consistent with autosomal recessive inheritance.
Mapping: By conducting a GWAS on 33 affected and 275 controls (each genotyped with a custom 50K SNP chip; Charlier et al., 2008, Nat Genet 40, 449-454), Sartelet et al. (2014) mapped this disorder to the proximal end of chromosome BTA25. Subsequent "Visual examination of the SNP genotypes defined a non-recombinant autozygous interval of 1.15 Mb (Bovine Genome assembly bTau6 (UMD3.1), chr25: 632,647-1,781,139) shared by all 33 cases and encompassing 82 annotated transcripts".
Molecular basis: Comparison of whole-genome sequence by Sartelet et al. (2014), from four affecteds and eight control Belgian Blue non-carriers, revealed three SNVs "[c2244G>C + c2248T>C + c2250C>A] located in exon 23 of the CLCN7 gene encoding the anion transport protein ClC-7". The first of these is synonymous, but the second and third jointly cause "a tyrosine to glutamine substitution (TAC>CAA: Y750Q)" in a highly conserved region of the protein. Subsequent genotyping for the two Y750Q missense mutations in "63 cases, 74 of their parents, 141 animals from 11 breeds other than BBCB, and 6,489 healthy BBCB animals" confirmed the causality of these mutations: "All cases were homozygous for the Y750Q mutation, while available parents and putative founder (Gabin) were all carriers. The mutation was absent in the non-BBCB cohort, and detected at a frequency of 5% (644 carriers) in BBCB controls. None of the genotyped controls was homozygous for the mutant (p=0.000026 under Hardy Weinberg equilibrium)."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: As reported by Sartelet et al. (2014), "Between 2008 and 2010, we collected biological material with pedigree records for 63 newborn calves with shared symptomatology: affected calves were mostly stillborn (70% of them), slightly premature (gestation length between 210 and 260 days, 73%), displayed a small body size (45%) and abdominal hydrops (58%), an abnormal skull shape (100%), inferior brachygnatism (100%), protruding tongue (81%) and gingival hamartomas of variable size (up to 15 cm diameter, 80%) located on the lower jaw . . . . All calves born alive were blind and consequently euthanized within days or weeks. At necropsy, we observed liver (82% . . . ) and kidney (59% . . . ) hypertrophies. Mothers of affected calves typically suffered from hydramnios, a condition commonly associated with impaired swallowing in the fetus".
Prevalence: Sartelet et al. (2014) reported that 10% of normal Belgian Blues are carriers of the pair of causal mutations.
Belgian Blue (Cattle) (VBO_0000139).
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|
|CLCN7||chloride channel, voltage-sensitive 7||Bos taurus||25||NC_037352.1 (1158734..1138163)||CLCN7||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|
|210||Belgian Blue (Cattle)||Osteopetrosis with gingival hamartomas||CLCN7||missense||Naturally occurring variant||ARS-UCD1.2||25||g.[1139611G>T; 1139613A>G]||c.[2248T>C;2250C>A]||p.(Y750Q)||2014||24159188||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.
|2021||Jacinto, J.G., Bolcato, M., Sheahan, B.J., Muscatello, L.V., Gentile, A., Avallone, G., Benazzi, C. :|
|Congenital tumours and tumour-like lesions in calves: a review. J Comp Pathol 184:84-94, 2021. Pubmed reference: 33894884. DOI: 10.1016/j.jcpa.2021.02.003.|
|2014||Sartelet, A., Stauber, T., Coppieters, W., Ludwig, C.F., Fasquelle, C., Druet, T., Zhang, Z., Ahariz, N., Cambisano, N., Jentsch, T.J., Charlier, C. :|
|A missense mutation accelerating the gating of the lysosomal Cl-/H+-exchanger ClC-7/Ostm1 causes osteopetrosis with gingival hamartomas in cattle. Dis Model Mech 7:119-28, 2014. Pubmed reference: 24159188. DOI: 10.1242/dmm.012500.|
- Created by Frank Nicholas on 28 Oct 2013
- Changed by Frank Nicholas on 28 Oct 2013
- Changed by Frank Nicholas on 15 Sep 2014
- Changed by Frank Nicholas on 16 Aug 2016
- Changed by Imke Tammen2 on 17 Aug 2021