{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T19:50:56Z","timestamp":1759693856532},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,9,11]],"date-time":"2003-09-11T00:00:00Z","timestamp":1063238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Joubert syndrome (JS) is a rare autosomal recessive malformation syndrome, involving dysgenesis of the cerebellar vermis with accompanying brainstem malformations (comprising the molar tooth sign). JS is characterized by hypotonia, developmental delay, intermittent hyperpnea and apnea, and abnormal eye movements. A single locus for JS was previously identified on 9q34 in a consanguineous family of Arabian origin. However, linkage to this locus has subsequently been shown to be rare. We have ascertained 35 JS pedigrees for haplotype segregation analysis of genetic loci for genes with a putative role in cerebellar development. We examined the <jats:italic>ZIC1<\/jats:italic> gene as a functional candidate for JS as <jats:italic>Zic1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> null mice have a phenotype reminiscent of JS. We undertook mutational analysis of <jats:italic>ZIC1<\/jats:italic> by standard mutational analysis (dideoxy\u2010fingerprinting (ddf)) of 47 JS probands, and fully sequenced the coding region in five of these probands. By these means, <jats:italic>ZIC1<\/jats:italic> was excluded from playing a causal role in most cases of JS as no disease\u2010associated mutations were identified. Further, linkage to the <jats:italic>ZIC1<\/jats:italic> genetic locus (3q24) was excluded in 21 of 35 pedigrees by haplotype segregation analysis of closely spaced markers. The remaining 14 of 35 pedigrees were consistent with linkage. However, this number does not significantly depart from that expected by random chance (16.5) for this cohort. Therefore, this systematic approach has been validated as a means to prioritize functional candidate genes and enables us to confine mutational analysis to only those probands whose segregation is consistent with linkage to any given locus. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.20438","type":"journal-article","created":{"date-parts":[[2004,2,18]],"date-time":"2004-02-18T17:13:54Z","timestamp":1077124434000},"page":"117-124","source":"Crossref","is-referenced-by-count":6,"title":["Joubert syndrome: A haplotype segregation strategy and exclusion of the zinc finger protein of cerebellum 1 (<i>ZIC1<\/i>) gene"],"prefix":"10.1002","volume":"125A","author":[{"given":"Craig L.","family":"Bennett","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa A.","family":"Parisi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa L.","family":"Eckert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huy M.","family":"Huynh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip F.","family":"Chance","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian A.","family":"Glass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,9,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.63051880.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-01-00284.1998"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-01-00218.2002"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/342975"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389202033350083"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10145"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/301769"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389901401007"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/380152a0"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1978.tb15307.x"},{"key":"e_1_2_6_12_1","first-page":"482","article-title":"Multilocus linkage analysis in humans: Detection of linkage and estimation of recombination","volume":"37","author":"Lathrop GM","year":"1985","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.4.2.97"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389701200703"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389901400906"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012235510600"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971003)72:1<59::AID-AJMG12>3.0.CO;2-T"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/302655"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320430415"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-973701"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389901401006"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.20438","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.20438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T13:24:21Z","timestamp":1697635461000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.20438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9,11]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2004,3]]}},"alternative-id":["10.1002\/ajmg.a.20438"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.20438","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9,11]]}}}