{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:47:34Z","timestamp":1772786854973,"version":"3.50.1"},"reference-count":30,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>Sonic hedgehog (SHH) plays an important role in defining the anterior\u2013posterior axis in the developing limbs. A highly conserved non-coding sequence about \u223c 1 Mb upstream from the <jats:italic>sonic hedgehog<\/jats:italic> gene (<jats:italic>SHH<\/jats:italic>) was shown to be a long range regulator for <jats:italic>SHH<\/jats:italic> expression in the limb bud. Point mutations within this non-coding regulatory region designated ZRS lead to ectopic expression of <jats:italic>Shh<\/jats:italic> in the anterior margin of the limb bud, as shown in mice, and cause the human triphalangeal thumb and polysyndactyly (TPT-PS) phenotype. Even though this association is well established, its molecular mechanism remains unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results:<\/jats:title>\n                  <jats:p>We investigated a large pedigree with variable TPT-PS. A single nucleotide exchange within the SHH limb regulator sequence was excluded, but locus specific microsatellite marker analyses confirmed a linkage to this region. Subsequently, array comparative genomic hybridisation (array CGH) was carried out using a submegabase whole human genome tiling path bacterial artificial chromosome (BAC) array revealing a microduplication in 7q36.3 in affected individuals. A duplicated region of 588,819 bp comprising the ZRS was identified by quantitative real-time polymerase chain reaction (qPCR) and direct sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>A novel microduplication in 7q36.3 results in a similar TPT-PS phenotype as caused by single nucleotide alterations in the ZRS, the limb specific <jats:italic>SHH<\/jats:italic> regulatory element. Duplications can be added to the growing list of mechanisms that cause abnormalities of long range transcriptional control.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2007.055699","type":"journal-article","created":{"date-parts":[[2008,1,4]],"date-time":"2008-01-04T20:45:28Z","timestamp":1199479528000},"page":"370-375","source":"Crossref","is-referenced-by-count":110,"title":["A microduplication of the long range SHH limb regulator (ZRS) is associated with triphalangeal thumb-polysyndactyly 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