{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:15:05Z","timestamp":1753892105935,"version":"3.41.2"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Preaxial polydactyly (PPD) is a common congenital abnormality with an incidence of 0.8\u20131.4% in Asians, characterized by the presence of extra digit(s) on the preaxial side of the hand or foot. PPD is genetically classified into four subtypes, PPD type I\u2013IV. Variants in six genes\/loci [including GLI family zinc finger 3 (<jats:italic>GLI3<\/jats:italic>), ZPA regulatory sequence (ZRS), and pre-ZRS region] have been identified in PPD cases. Among these loci, ZRS is, perhaps, the most special and well known, but most articles only reported one or a few cases. There is a lack of reports on the ZRS-variant frequency in patients with PPD. In this study, we recruited 167 sporadic or familial cases (including 154 sporadic patients and 13 families) with PPD from Central-South China and identified four ZRS variants in four patients (2.40%, 4\/167), including two novel variants (ZRS131A &amp;gt; T\/chr7:g.156584439A &amp;gt; T and ZRS474C &amp;gt; G\/chr7:g.156584096C &amp;gt; G) and two known variants (ZRS428T &amp;gt; A\/chr7:g.156584142T &amp;gt; A and ZRS619C &amp;gt; T\/chr7:g.156583951C &amp;gt; T). ZRS131A &amp;gt; T and ZRS428T &amp;gt; A were detected in PPD I cases and ZRS474C &amp;gt; G and ZRS619C &amp;gt; T combinedly acted to cause PPD II. The detectable rate of ZRS variants in PPD I was 1.60% (2\/125), while PPD II was significantly higher (9.52%, 2\/21). Three bilateral PPD cases harbored ZRS variants (13.64%, 3\/22), suggesting that bilateral PPD was more possibly caused by genetic etiologies. This study identified two novel ZRS variants, further confirmed the association between ZRS and PPD I and reported a rare PPD II case resulted from the compound heterozygote of ZRS. This investigation preliminarily evaluated a ZRS variants rate in patients with PPD and described the general picture of PPD in Central-South China.<\/jats:p>","DOI":"10.3389\/fped.2022.797978","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T08:43:20Z","timestamp":1652690600000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["ZPA Regulatory Sequence Variants in Chinese Patients With Preaxial Polydactyly: Genetic and Clinical 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