Recently, mutations in a noncoding evolutionary conserved sequence 500 bp upstream of the ZRS, termed the pre-ZRS (pZRS), have been associated with polydactyly in dogs and humans.
In the present study, four genomic regions (exons of GLI3, SHH, and noncoding sequences of preZRS and ZRS) involved in hedgehog (Hh) signaling pathway were sequenced for 102 unrelated Chinese children with nonsyndromic polydactyly.
The plausible mutation rs80659072 in the zone of polarizing activity regulatory sequence (ZRS) in chickens was an essential but not sufficient condition for polydactyly and polyphalangy in Beijing You chickens.
The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly.
Point mutations and duplications of the ZRS lead to a variable phenotype of preaxial polydactyly/triphalangeal thumb, tibial hypoplasia, radial ray deficiency, and type IV familial syndactyly (syndactyly of all digits with polydactyly).
Therefore, we sequenced the ZRS in 101 heterozygous and 30 unaffected (wild-type) individuals to establish the relevance of this region to the Po condition in the UCD-Po.003 congenic line.
To date, 19 point mutations, 10 duplications and 1 triplication of the ZRS associated with those pre-axial polydactylies have been reported in humans, mice, cats and chickens.