OMIA:001944-9615 : Spondylocostal dysostosis, autosomal recessive in Canis lupus familiaris
Categories: Skeleton phene (incl. short stature & teeth)
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 613686 (trait) , 608059 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive lethal
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2015
Species-specific symbol: SCD
Species-specific description: Also called Comma defect (Willet et al., 2015), "due to the gross anatomical shape of the abnormal pups".
Inheritance: The three-generation pedigree reported by Willet et al. (2015) was consistent with autosomal recessive inheritance, which was confirmed with genotyping of the causal mutation in the extended family of the affected dogs.
Mapping: By conducting a GWAS on a family comprising normal parents plus 3 affected and 5 normal offspring, each genotyped with the Canine HD BeadChip (yielding 73,921 informative SNPs), Willet et al. (2015) mapped this disorder to a 25 Mb region on chromosome CFA5:29.84Mb–45.26Mb.
Molecular basis: Comparative analysis by Willet et al. (2015), based on location and phenotype in the mouse, revealed 19 positional comparative candidate genes. Whole-genome sequencing of two of the affected sibs revealed 5 candidate functional mutations, which were subsequently narrowed down to the causal mutation, a "guanine deletion at CFA5:35,940,090 (CFA5:32,945,846 in canFam3.1) within exon 2 of HES7 (c.126delG) . . . [which] introduces a frameshift mutation, causing alteration from the 43rd amino acid onwards and resulting in a premature termination codon in place of the 66th amino acid (p.(Thr43ProfsTer24))". Genotyping for this mutation in 133 dogs, including the three affected dogs and extended family members, confirmed this as the causal mutation.
Clinical features: As reported by Willet et al. (2015), "The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number." Also, "The three affected pups were born stillborn or died within hours of birth. Gross external examination of the pups by the attending veterinarian revealed a reduction in body length compared with normal littermates (data not available). The hindquarters of affected pups were reduced in size compared to the forequarters, giving an overall comma-like morphology to the body". One of the affected samples had umbilical hernia and another had a cleft hard palate.
Prevalence: Willet et al. (2015) tested 127 Miniature Schnauzers and six Standard Schnauzers for the deletion. Only the three affected pups tested homozygous for the mutant allele, and four family members tested heterozygous, giving an estimated allele frequency of 0.04 for the eastern Australian population tested. Carrier imported family members from Sweden and Argentina suggest that the allele may be globally dispersed.
Breed: Miniature Schnauzer.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|HES7||hes family bHLH transcription factor 7||Canis lupus familiaris||5||NC_051809.1 (33052693..33047237)||HES7||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|
|535||Miniature Schnauzer||Spondylocostal dysostosis, autosomal recessive||HES7||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||5||g.32945846del||c.126delG||p.(T43Pfs*24)||2015||25659135|
|2015||Willet, C.E., Makara, M., Reppas, G., Tsoukalas, G., Malik, R., Haase, B., Wade, C.M. :|
|Canine Disorder Mirrors Human Disease: Exonic Deletion in HES7 Causes Autosomal Recessive Spondylocostal Dysostosis in Miniature Schnauzer Dogs. PLoS One 10:e0117055, 2015. Pubmed reference: 25659135 . DOI: 10.1371/journal.pone.0117055.|
- Created by Frank Nicholas on 08 Feb 2015
- Changed by Frank Nicholas on 08 Feb 2015
- Changed by Frank Nicholas on 10 Feb 2015
- Changed by Frank Nicholas on 04 Apr 2017
- Changed by Cali Willet on 02 Jun 2017
- Changed by Frank Nicholas on 02 Jun 2017