{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:44:53Z","timestamp":1791121493448,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,1,6]],"date-time":"2015-01-06T00:00:00Z","timestamp":1420502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>During limb development, the spatio\u2010temporal expression of <jats:italic>sonic hedgehog<\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">SHH<\/jats:styled-content><\/jats:italic>) is driven by the Zone of polarizing activity Regulatory Sequence (<jats:styled-content style=\"fixed-case\">ZRS<\/jats:styled-content>), located 1 megabase upstream from <jats:italic><jats:styled-content style=\"fixed-case\">SHH<\/jats:styled-content><\/jats:italic>. Gain\u2010of\u2010function mutations of this enhancer, which cause ectopic expression of <jats:italic><jats:styled-content style=\"fixed-case\">SHH<\/jats:styled-content><\/jats:italic>, are known to be responsible for congenital limb malformations with variable expressivity, ranging from preaxial polydactyly or triphalangeal thumbs to polysyndactyly, which may also be associated with mesomelic deficiency. In this report, we describe a patient affected with mirror\u2010image polydactyly of the four extremities and bilateral tibial deficiency. The proband's father had isolated preaxial polydactyly type <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">PPD2<\/jats:styled-content>). Using Sanger sequencing, a <jats:styled-content style=\"fixed-case\">ZRS<\/jats:styled-content> point mutation (NC_000007.14, g.<jats:styled-content style=\"fixed-case\">156584153A<\/jats:styled-content>&gt;G, <jats:styled-content style=\"fixed-case\">UCSC<\/jats:styled-content>, Build hg.19) was only identified in the patient. However, pyrosequencing analysis enabled the detection of a 10% somatic mosaic in the blood and saliva from the father. To our knowledge, this is the first description of a <jats:styled-content style=\"fixed-case\">ZRS<\/jats:styled-content> mosaic mutation. This report highlights the complexity of genotype\u2013phenotype correlation in <jats:italic><jats:styled-content style=\"fixed-case\">ZRS<\/jats:styled-content><\/jats:italic>\u2010associated syndromes and the importance of detecting somatic mosaicism for accurate genetic counselling.<\/jats:p>","DOI":"10.1111\/cge.12534","type":"journal-article","created":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T06:42:14Z","timestamp":1415601734000},"page":"479-483","source":"Crossref","is-referenced-by-count":11,"title":["Intrafamilial variability of <i><scp>ZRS<\/scp><\/i>\u2010associated syndrome: characterization of a mosaic <i><scp>ZRS<\/scp><\/i> mutation by pyrosequencing"],"prefix":"10.1111","volume":"88","author":[{"given":"C.","family":"Vanlerberghe","sequence":"first","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, Centre de Biologie Pathologie CHRU  Lille France"},{"name":"Clinique de G\u00e9n\u00e9tique m\u00e9dicale, H\u00f4pital Jeanne de Flandre CHRU  Lille France"},{"name":"RADEME Research Team for Rare Metabolic and Developmental Diseases Universit\u00e9 Lille 2  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Faivre","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique clinique H\u00f4pital d'enfants  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Petit","sequence":"additional","affiliation":[{"name":"Clinique de G\u00e9n\u00e9tique m\u00e9dicale, H\u00f4pital Jeanne de Flandre CHRU  Lille France"},{"name":"RADEME Research Team for Rare Metabolic and Developmental Diseases Universit\u00e9 Lille 2  Lille France"},{"name":"Facult\u00e9 de M\u00e9decine Universit\u00e9 Lille II  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Fruchart","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, Centre de Biologie Pathologie CHRU  Lille France"},{"name":"RADEME Research Team for Rare Metabolic and Developmental Diseases Universit\u00e9 Lille 2  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.\u2010S.","family":"Jourdain","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, Centre de Biologie Pathologie CHRU  Lille France"},{"name":"RADEME Research Team for Rare Metabolic and Developmental Diseases Universit\u00e9 Lille 2  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Clavier","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence national maladies rares des malformations des membres et de l'arthrogrypose chez l'enfant Saint Maurice H\u00f4pital Saint Maurice  Saint Maurice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Gay","sequence":"additional","affiliation":[{"name":"Service de p\u00e9diatrie Centre Hospitalier William Morey  Chalon sur Sa\u00f4ne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Manouvrier\u2010Hanu","sequence":"additional","affiliation":[{"name":"Clinique de G\u00e9n\u00e9tique m\u00e9dicale, H\u00f4pital Jeanne de Flandre CHRU  Lille France"},{"name":"RADEME Research Team for Rare Metabolic and Developmental Diseases Universit\u00e9 Lille 2  Lille France"},{"name":"Facult\u00e9 de M\u00e9decine Universit\u00e9 Lille II  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Escande","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, Centre de Biologie Pathologie CHRU  Lille France"},{"name":"RADEME Research Team for Rare Metabolic and Developmental Diseases Universit\u00e9 Lille 2  Lille 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