{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:15Z","timestamp":1753869735628,"version":"3.41.2"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,20]],"date-time":"2019-07-20T00:00:00Z","timestamp":1563580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Research Council of Lithuania","doi-asserted-by":"crossref","award":["S-MIP-17-19\/LSS-150000-1179"],"award-info":[{"award-number":["S-MIP-17-19\/LSS-150000-1179"]}],"id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Preaxial polydactyly type IV, also referred as polysyndactyly, has been described in a few syndromes. We present three generations of a family with preaxial polydactyly type IV and other clinical features of Greig cephalopolysyndactyly syndrome (GCPS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Sequencing analysis of the <jats:italic>GLI3<\/jats:italic> coding region identified a novel donor splice site variant NC_000007.14(NM_000168.6):c.473+3A&gt;T in the proband and the same pathogenic variant was subsequently identified in other affected family members. Functional analysis based on Sanger sequencing of the proband's complementary DNA (cDNA) sample revealed that the splice site variant c.473+3A&gt;T disrupts the original donor splice site, thus leading to exon 4 skipping. Based on further in silico analysis, this pathogenic splice site variant consequently results in a truncated protein NP_000159.3:p.(His123Argfs*57), which lacks almost all functionally important domains. Therefore, functional cDNA analysis confirmed that the haploinsufficiency of the <jats:italic>GLI3<\/jats:italic> is the cause of GCPS in the affected family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite the evidence provided, pathogenic variants in the <jats:italic>GLI3<\/jats:italic> do not always definitely correlate with syndromic or nonsyndromic clinical phenotypes associated with this gene. For this reason, further transcriptomic and proteomic evaluation could be suggested.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.878","type":"journal-article","created":{"date-parts":[[2019,7,20]],"date-time":"2019-07-20T08:08:36Z","timestamp":1563610116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel <i>GLI3<\/i> variant causes Greig cephalopolysyndactyly syndrome in three generations of a Lithuanian family"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3110-4059","authenticated-orcid":false,"given":"Evelina","family":"Siavrien\u0117","sequence":"first","affiliation":[{"name":"Department of Human and Medical Genetics, Faculty of Medicine, Institute of Biomedical Sciences Vilnius University Vilnius Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Violeta","family":"Mik\u0161tien\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Faculty of Medicine, Institute of Biomedical Sciences Vilnius University Vilnius Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darius","family":"Radzevi\u010dius","sequence":"additional","affiliation":[{"name":"The Children's Hospital Affiliate of Vilnius University Hospital Santaros Klinikos Vilnius Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u017divil\u0117","family":"Mald\u017eien\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Faculty of Medicine, Institute of Biomedical Sciences Vilnius University Vilnius Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tautvydas","family":"Ran\u010delis","sequence":"additional","affiliation":[{"name":"Department 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