Polydactyly

Polydactyly is a congenital condition characterized by an increased number of digits (more commonly on the forelimbs) and changes in their shape. It results from abnormal regulation of the developmental gene Sonic Hedgehog (SHH). This defect is caused by mutations in the ZRS regulatory sequence, which controls the expression of the SHH gene during limb bud development. Polydactyly generally does not cause serious health problems; however, loosely attached extra digits should be surgically removed because of the increased risk of injury or snagging.

Several mutations associated with polydactyly have been identified in the ZRS regulatory region of the LMBR1 gene. In the Maine Coon, the mutation g.169532844T>C (PdHw/Hemingway) has been described, while the mutations g.169532842T>A (PdUK1) and g.169533066C>G (PdUK2) have been identified in other cat breeds.

This test detects all three of the above mutations. However, a study published in 2020 in Maine Coon cats demonstrated that a substantial proportion of polydactylous individuals do not carry any of these three variants. The authors also analyzed other known regulatory regions involved in limb development but did not identify an additional causative mutation. These findings demonstrate that feline polydactyly is a genetically heterogeneous trait and that additional, as yet unidentified, genetic variants may also be responsible.

A negative test result therefore does not exclude genetically determined polydactyly. It only indicates that the three currently known and routinely tested mutations in the ZRS regulatory region of the LMBR1 gene were not detected in the tested individual.

These mutations are inherited in an autosomal dominant manner with incomplete penetrance and variable expressivity. This means that a single copy of the mutated allele inherited from one parent is sufficient for the trait to occur, although the degree of expression may vary considerably among individuals. Genetic testing enables accurate determination of an animal's genotype and provides breeders with a valuable tool for responsible breeding and for reducing the unintentional breeding of affected animals.

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References:

Lettice, LA., Hill, AE., Devenney, PS., Hill, RE. : Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum Mol Genet 17:978-85, 2008. Pubmed reference: 18156157

Hamelin A., Conchou F., Fusellier M. et al. Genetic heterogeneity of polydactyly in Maine Coon cats. Journal of Feline Medicine and Surgery. 2020;22(12):1103–1113. PMID: 32067556