{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:46:32Z","timestamp":1760233592288,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["SAF2016-75946R"],"award-info":[{"award-number":["SAF2016-75946R"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n Biomedica en Red de Enfermedades Raras (CIBERER)","award":["ACCI2018-15"],"award-info":[{"award-number":["ACCI2018-15"]}]},{"name":"Associaci\u00f3 S\u00edndrome Opitz C","award":["-"],"award-info":[{"award-number":["-"]}]},{"DOI":"10.13039\/501100010552","name":"Departament de Salut, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["PERIS SLT002\/16\/00174"],"award-info":[{"award-number":["PERIS SLT002\/16\/00174"]}],"id":[{"id":"10.13039\/501100010552","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We present a Turkish family with two cousins (OC15 and OC15b) affected with syndromic developmental delay, microcephaly, and trigonocephaly but with some phenotypic traits distinct between them. OC15 showed asymmetrical skeletal defects and syndactyly, while OC15b presented with a more severe microcephaly and semilobal holoprosencephaly. All four progenitors were related and OC15 parents were consanguineous. Whole Exome Sequencing (WES) analysis was performed on patient OC15 as a singleton and on the OC15b trio. Selected variants were validated by Sanger sequencing. We did not identify any shared variant that could be associated with the disease. Instead, each patient presented a de novo heterozygous variant in a different gene. OC15 carried a nonsense mutation (p.Arg95*) in PORCN, which is a gene responsible for Goltz-Gorlin syndrome, while OC15b carried an indel mutation in ZIC2 leading to the substitution of three residues by a proline (p.His404_Ser406delinsPro). Autosomal dominant mutations in ZIC2 have been associated with holoprosencephaly 5. Both variants are absent in the general population and are predicted to be pathogenic. These two de novo heterozygous variants identified in the two patients seem to explain the major phenotypic alterations of each particular case, instead of a homozygous variant that would be expected by the underlying consanguinity.<\/jats:p>","DOI":"10.3390\/ijms22041549","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T12:02:10Z","timestamp":1612440130000},"page":"1549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["De Novo PORCN and ZIC2 Mutations in a Highly Consanguineous Family"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2260-9664","authenticated-orcid":false,"given":"Laura","family":"Castilla-Vallmanya","sequence":"first","affiliation":[{"name":"IBUB, IRSJD, and CIBERER (ISCIII), Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Semra","family":"G\u00fcrsoy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics, Dr. Behcet Uz Children\u2019s Hospital, Izmir 35210, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6zlem","family":"Giray-Bozkaya","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-6549","authenticated-orcid":false,"given":"Aina","family":"Prat-Planas","sequence":"additional","affiliation":[{"name":"IBUB, IRSJD, and CIBERER (ISCIII), Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Bullich","sequence":"additional","affiliation":[{"name":"CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Matalonga","sequence":"additional","affiliation":[{"name":"CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8881-0264","authenticated-orcid":false,"given":"M\u00f3nica","family":"Centeno-Pla","sequence":"additional","affiliation":[{"name":"IBUB, IRSJD, and CIBERER (ISCIII), Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5006-8140","authenticated-orcid":false,"given":"Raquel","family":"Rabionet","sequence":"additional","affiliation":[{"name":"IBUB, IRSJD, and CIBERER (ISCIII), Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-2590","authenticated-orcid":false,"given":"Daniel","family":"Grinberg","sequence":"additional","affiliation":[{"name":"IBUB, IRSJD, and CIBERER (ISCIII), Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Balcells","sequence":"additional","affiliation":[{"name":"IBUB, IRSJD, and CIBERER (ISCIII), Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roser","family":"Urreizti","sequence":"additional","affiliation":[{"name":"IBUB, IRSJD, and CIBERER (ISCIII), Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. 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