OMIA:001509-9615 : Geleophysic dysplasia, ADMATSL2-related in Canis lupus familiaris (dog)

Categories: Skeleton phene (incl. short stature & teeth)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 231050 (trait) , 612277 (gene)

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]

Breed: Beagle (Dog) (VBO_0200131).
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:

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 Year Published PubMed ID(s) Acknowledgements
60 Beagle (Dog) 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

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001509-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

Edit History

  • Created by Frank Nicholas on 26 Oct 2010
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 28 Nov 2012
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Tosso Leeb on 28 Jan 2016
  • Changed by Imke Tammen2 on 17 Apr 2021
  • Changed by Imke Tammen2 on 03 Jun 2022