{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:44:55Z","timestamp":1791121495256,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T00:00:00Z","timestamp":1392595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KL 2158\/2-2"],"award-info":[{"award-number":["KL 2158\/2-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p>Laurin\u2010Sandrow syndrome (<jats:styled-content style=\"fixed-case\">LSS<\/jats:styled-content>) is a rare autosomal dominant disorder characterized by polysyndactyly of hands and\/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. The genetic basis of <jats:styled-content style=\"fixed-case\">LSS<\/jats:styled-content> is currently unknown. <jats:styled-content style=\"fixed-case\">LSS<\/jats:styled-content> shows phenotypic overlap with Haas\u2010type polysyndactyly (<jats:styled-content style=\"fixed-case\">HTS<\/jats:styled-content>) regarding the digital phenotype. Here we report on five unrelated families with overlapping microduplications encompassing the <jats:italic>Sonic hedgehog (<jats:styled-content style=\"fixed-case\">SHH<\/jats:styled-content>)<\/jats:italic> limb enhancer ZPA regulatory sequence (<jats:styled-content style=\"fixed-case\">ZRS<\/jats:styled-content>) on chromosome 7q36. Clinically, the patients show polysyndactyly phenotypes and various types of lower limb malformations ranging from syndactyly to mirror image polydactyly with duplications of the fibulae. We show that larger duplications of the <jats:styled-content style=\"fixed-case\">ZRS<\/jats:styled-content> region (&gt;80\u2009kb) are associated with <jats:styled-content style=\"fixed-case\">HTS<\/jats:styled-content>, whereas smaller duplications (&lt;80\u2009kb) result in the <jats:styled-content style=\"fixed-case\">LSS<\/jats:styled-content> phenotype. On the basis of our data, the latter can be clearly distinguished from <jats:styled-content style=\"fixed-case\">HTS<\/jats:styled-content> by the presence of mirror image polysyndactyly of the feet with duplication of the fibula. Our results expand the clinical phenotype of the <jats:styled-content style=\"fixed-case\">ZRS<\/jats:styled-content>\u2010associated syndromes and suggest that smaller duplications (&lt;80\u2009kb) are associated with a more severe phenotype. In addition, we show that these small microduplications within the <jats:styled-content style=\"fixed-case\">ZRS<\/jats:styled-content> region are the underlying genetic cause of Laurin\u2010Sandrow syndrome.<\/jats:p>","DOI":"10.1111\/cge.12352","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T17:13:02Z","timestamp":1390497182000},"page":"318-325","source":"Crossref","is-referenced-by-count":64,"title":["Microduplications encompassing the Sonic hedgehog limb enhancer <scp>ZRS<\/scp> are associated with Haas\u2010type polysyndactyly and Laurin\u2010Sandrow syndrome"],"prefix":"10.1111","volume":"86","author":[{"given":"S.","family":"Lohan","sequence":"first","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max Planck Institute for Molecular Genetics Research Group Mundlos Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Spielmann","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max Planck Institute for Molecular Genetics Research Group Mundlos Berlin Germany"},{"name":"Berlin\u2010Brandenburg School for Regenerative Therapies (BSRT) Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.C.","family":"Doelken","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Fl\u00f6ttmann","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory National Institute for Biotechnology and Genetic Engineering Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.M.","family":"Baig","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory National Institute for Biotechnology and Genetic Engineering Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Wajid","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory National Institute for Biotechnology and Genetic Engineering Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"H\u00fclsemann","sequence":"additional","affiliation":[{"name":"Handchirurgie Kinderkrankenhaus Wilhelmstift Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Habenicht","sequence":"additional","affiliation":[{"name":"Handchirurgie Kinderkrankenhaus Wilhelmstift Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.W.","family":"Kjaer","sequence":"additional","affiliation":[{"name":"Wilhelm Johannsen Centre for Functional Genome Research University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.J.","family":"Patil","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Metabolic Diagnostics and Research Narayana Hrudayalaya Hospitals Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.M.","family":"Girisha","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Kasturba Medical College, Manipal University Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.H.","family":"Abarca\u2010Barriga","sequence":"additional","affiliation":[{"name":"Genetic Instituto Nacional de Salud del Ni\u00f1o Lima Peru"},{"name":"Centro de Investigaci\u00f3n de Gen\u00e9tica Humana Wi\u00f1ay Gen\u00e9tica Lima Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mundlos","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max Planck Institute for Molecular Genetics Research Group Mundlos Berlin Germany"},{"name":"Berlin\u2010Brandenburg School for Regenerative Therapies (BSRT) Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Klopocki","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Institute for Human Genetics, Biozentrum Universit\u00e4t W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2012.03.012"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg180"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.12.010"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.055699"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21142"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.057646"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-196446010-00014"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-197052020-00021"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010122)98:3<210::AID-AJMG1085>3.0.CO;2-7"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30820"},{"issue":"3","key":"e_1_2_6_12_1","first-page":"3","article-title":"Laurin\u2010Sandrow syndrome: a case report. Genetic clinics","volume":"6","author":"Patil SJ","year":"2013","journal-title":"Newsl Indian Acad Med Genet"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.11.006"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32740"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-013-2071-y"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.264"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00192"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-082410-101404"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0809-862"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.001"},{"key":"e_1_2_6_21_1","first-page":"S0959","article-title":"CNVs of noncoding cis\u2010regulatory elements in human disease","author":"Spielmann M","year":"2013","journal-title":"Curr Opin Genet Dev"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201200178"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21615"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.014"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01613"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12352","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12352","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T15:19:54Z","timestamp":1696346394000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,17]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1111\/cge.12352"],"URL":"https:\/\/doi.org\/10.1111\/cge.12352","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,17]]}}}