OMIA 001509-9615 : Musladin-Lueke syndrome in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 231050

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2010

Species-specific name: 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."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ADAMTSL2 ADAMTS-like 2 Canis lupus familiaris 9 NC_006591.3 (49925738..49958870) ADAMTSL2 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
Beagle Musladin-Lueke syndrome ADAMTSL2 missense 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

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.
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