De novo PORCN and ZIC2 mutations in a highly consanguineous family
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- dc.contributor.author Castilla-Vallmanya, Laura
- dc.contributor.author Gürsoy, Semra
- dc.contributor.author Bozkaya, Özlem Giray
- dc.contributor.author Prats-Planas, Aina
- dc.contributor.author Bullich, Gemma
- dc.contributor.author Matalonga, Leslie
- dc.contributor.author Centeno-Pla, Mónica
- dc.contributor.author Rabionet Janssen, Raquel
- dc.contributor.author Grinberg, Daniel
- dc.contributor.author Balcells, Susana
- dc.contributor.author Urreizti, Roser
- dc.date.accessioned 2022-05-16T10:33:59Z
- dc.date.available 2022-05-16T10:33:59Z
- dc.date.issued 2021
- dc.description.abstract 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.
- dc.description.sponsorship Funding was from the Spanish Ministerio de Ciencia e Innovación (SAF2016-75946R), CIBERER (ACCI2018-15), Associació Síndrome Opitz C. Departament de Salut de la Generalitat de Catalunya, PERIS SLT002/16/00174, URD-Cat (Implementació de la Medicina Personalitzada basada en la Genòmica en Malalties Minoritàries Neurològiques no Diagnosticades), 2017–2019
- dc.format.mimetype application/pdf
- dc.identifier.citation Castilla-Vallmanya L, Gürsoy S, Giray-Bozkaya Ö, Prat-Planas A, Bullich G, Matalonga L et al. De novo PORCN and ZIC2 mutations in a highly consanguineous family. Int J Mol Sci. 2021 Feb 4;22(4):1549. DOI:10.3390/ijms22041549
- dc.identifier.doi http://dx.doi.org/10.3390/ijms22041549
- dc.identifier.issn 1661-6596
- dc.identifier.uri http://hdl.handle.net/10230/53091
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75946R
- dc.rights © 2021 by Laura Castillo-Vallmanya et al. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Genètica mèdica
- dc.subject.other Consanguinitat
- dc.subject.other Tractament dels trastorns del neurodesenvolupament
- dc.title De novo PORCN and ZIC2 mutations in a highly consanguineous family
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion