OMIA:001509-9615 : Geleophysic dysplasia, ADMATSL2-related in Canis lupus familiaris
Categories: Skeleton phene (incl. short stature & teeth)
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 231050 (trait) , 612277 (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: 2010
Cross-species summary: Renamed from Musladin-Lueke syndrome [3/6/2022]
Species-specific name: Musladin-Lueke syndrome, Chinese beagle syndrome
Species-specific symbol: MLS
History: As reported by Bader et al. (2010), this disorder was "originally called “Chinese beagle syndrome” in the lay literature, and subsequently renamed after two noted beagle breeders, Musladin and Lueke"; see Musladin et al. (1990, 1998).
Mapping: By conducting a genome scan on 6 affecteds and 39 control Beagles, each genotyped for 719 microsatellites in a case-control design, Bader et al. (2010) mapped the disorder to a region on chromosome CFA9.
Molecular basis: Fine-mapping followed by sequencing of likely positional candidate genes resulted in Bader et al (2010) identifying the causal mutation as a missense mutation in ADAMTSL2: "(c.660C>T) predicted a non-synonymous change, converting an arginine to a cysteine at codon 221 (R221C), occurred in a highly conserved stretch of residues, and was computationally predicted to negatively impact protein structure and function". The publication of Bader et al. 2010 probably had an incorrect numbering of the cDNA in their variant designation. The correct variant designation should read XM_003639308.3:c.661C>T; p.Arg221Cys.
Clinical features: As reported by Bader et al. (2010), this disorder "is characterized by short stature, thick, taut skin, and severely restricted joint mobility . . . Affected dogs also have broad skulls with wide-set slanted eyes, creased ears, a hopping, “tip-toe” gait, and pleasant temperaments." Additionally, cardiac disease has been reported as possibly associated with Muscladin-Lueke syndrome, but reports are inconsistent (Packer et al., 2017). [IT thanks DVM student Elizabeth Polley for contributions to this entry in April 2022]
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ADAMTSL2||ADAMTS-like 2||Canis lupus familiaris||9||NC_051813.1 (50799767..50833236)||ADAMTSL2||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|
|60||Beagle||Musladin-Lueke syndrome||ADAMTSL2||missense||Naturally occurring variant||CanFam3.1||9||g.49931561C>T||c.661C>T||p.(R221C)||2010||20862248||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
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.
|2017||Packer, R.A., Logan, M.A., Guo, L.T., Apte, S.S., Bader, H., O'Brien, D.P., Johnson, G., Shelton, G.D. :|
|Clinical phenotype of Musladin-Lueke syndrome in 2 Beagles. J Vet Intern Med 31:532-538, 2017. Pubmed reference: 28158899 . DOI: 10.1111/jvim.14654.|
|2010||Bader, HL., Ruhe, AL., Wang, LW., Wong, AK., Walsh, KF., Packer, RA., Mitelman, J., Robertson, KR., O'Brien, DP., Broman, KW., Shelton, GD., Apte, SS., Neff, MW. :|
|An ADAMTSL2 founder mutation causes Musladin-Lueke Syndrome, a heritable disorder of beagle dogs, featuring stiff skin and joint contractures. PLoS One 5:, 2010. Pubmed reference: 20862248 . DOI: 10.1371/journal.pone.0012817.|
|1998||Musladin, J.M., Musladin, A.C., Lueke, A. :|
|"The New Beagle", Howell Book House, New York (2nd edn) :, 1998.|
|1990||Musladin, J.M., Musladin, A.C., Lueke, A. :|
|"The New Beagle", Howell Book House, New York :, 1990.|
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