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

Disease-related: 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: