OMIA 001595-9940 : Brachygnathia, cardiomegaly and renal hypoplasia syndrome in Ovis aries

Possibly relevant human trait(s) and/or gene(s) (MIM number): 612921

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: Short stature syndrome similar to 3M syndrome in humans

Species-specific symbol: BCRHS

History: This lethal disorder was first described by Shariflou et al. (2011). Its clinical signs are well described by its name.

Mapping: By genotyping 10 affected and 27 control Merinos, each with the Illumina Ovine SNP50 BeadChip (yielding 40,899 informative SNPs), Shariflou et al. (2013) used GWAS and homozygosity mapping to locate this disorder to "a region comprising 20 consecutive SNPs spanning 1.1 Mb towards the distal end of chromosome OAR2".

Molecular basis: Woolley et al. (2020) identified eight positional candidate genes in the interval identified by Shariflou et al. (2013) and "Obscurin like cytoskeletal adaptor 1 (OBSL1) was selected as a strong positional candidate gene based on gene function and the resulting phenotypes observed in humans with mutations in this gene. Whole genome sequencing of an affected lamb (BCRHS3) identified a likely causal variant ENSOARG00000020239:g.220,472,248delC within OBSL1. Sanger sequencing of seven affected, six obligate carrier, two phenotypically unaffected animals from the original flock and one unrelated control animal validated the variant." The likely disease-causing variant is predicted to result in a frameshift (p.(Val573Trpfs*119)) in the OBSL1 protein.

Clinical features: Affected lambs are stillborn with various congenital defects as reflected in the name of the disease, as well as short stature, a short and broad cranium, a small thoracic cavity, thin ribs and brachysternum. The BCRHS phenotype shows similarity to certain human short stature syndromes, in particular the human 3M syndrome-2.

Breed: Merino.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
OBSL1 obscurin-like 1 Ovis aries 2 NC_040253.1 (236307633..236285750) OBSL1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Merino Brachygnathia, cardiomegaly and renal hypoplasia syndrome OBSL1 deletion, small (<=20) Ovis aries Oar_v3.1 2 g.220,472,248delC c.1,716delC p.(Val573Trpfs*119) XM_027965226.1:c.1,716delC 2020 32933480

References


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.
2020 Woolley, S.A., Hayes, S.E., Shariflou, M.R., Nicholas, F.W., Willet, C.E., O'Rourke, B.A., Tammen, I. :
Molecular basis of a new ovine model for human 3M syndrome-2. BMC Genet 21:106, 2020. Pubmed reference: 32933480. DOI: 10.1186/s12863-020-00913-8.
2013 Shariflou, M.R., Wade, C.M., Kijas, J., McCulloch, R., Windsor, P.A., Tammen, I., Nicholas, F.W. :
Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in Merino sheep maps to a 1.1-megabase region on ovine chromosome OAR2. Anim Genet 44:231-3, 2013. Pubmed reference: 22762779. DOI: 10.1111/j.1365-2052.2012.02392.x.
2011 Shariflou, M., Wade, C., Windsor, P., Tammen, I., James, J.W., Nicholas, F.W. :
Lethal genetic disorder in Poll Merino/Merino sheep in Australia. Aust Vet J 89:254-9, 2011. Pubmed reference: 21696373. DOI: 10.1111/j.1751-0813.2011.00789.x.

Edit History


  • Created by Frank Nicholas on 03 Aug 2011
  • Changed by Frank Nicholas on 06 Jul 2012
  • Changed by Frank Nicholas on 26 Aug 2013
  • Changed by Imke Tammen2 on 18 Sep 2020
  • Changed by Imke Tammen2 on 19 Sep 2020