dc.contributor.author
Sczakiel, Henrike Lisa
dc.contributor.author
Hülsemann, Wiebke
dc.contributor.author
Holtgrewe, Manuel
dc.contributor.author
Abad‐Perez, Angela Teresa
dc.contributor.author
Elsner, Jonas
dc.contributor.author
Schwartzmann, Sarina
dc.contributor.author
Horn, Denise
dc.contributor.author
Spielmann, Malte
dc.contributor.author
Mundlos, Stefan
dc.contributor.author
Mensah, Martin Atta
dc.date.accessioned
2022-12-07T14:34:06Z
dc.date.available
2022-12-07T14:34:06Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/37214
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-36926
dc.description.abstract
Loss of function variants of GLI3 are associated with a variety of forms of polysyndactyly: Pallister-Hall syndrome (PHS), Greig-Cephalopolysyndactyly syndrome (GCPS), and isolated polysyndactyly (IPD). Variants affecting the N-terminal and C-terminal thirds of the GLI3 protein have been associated with GCPS, those within the central third with PHS. Cases of IPD have been attributed to variants affecting the C-terminal third of the GLI3 protein. In this study, we further investigate these genotype-phenotype correlations. Sequencing of GLI3 was performed in patients with clinical findings suggestive of a GLI3-associated syndrome. Additionally, we searched the literature for reported cases of either manifestation with mutations in the GLI3 gene. Here, we report 48 novel cases from 16 families with polysyndactyly in whom we found causative variants in GLI3 and a review on 314 previously reported GLI3 variants. No differences in location of variants causing either GCPS or IPD were found. Review of published data confirmed the association of PHS and variants affecting the GLI3 protein's central third. We conclude that the observed manifestations of GLI3 variants as GCPS or IPD display different phenotypic severities of the same disorder and propose a binary division of GLI3-associated disorders in either PHS or GCPS/polysyndactyly.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
genotype-phenotype correlations
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
GLI3 variants causing isolated polysyndactyly are not restricted to the protein's C-terminal third
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1111/cge.14059
dcterms.bibliographicCitation.journaltitle
Clinical Genetics
dcterms.bibliographicCitation.number
6
dcterms.bibliographicCitation.originalpublishername
Wiley
dcterms.bibliographicCitation.pagestart
758
dcterms.bibliographicCitation.pageend
765
dcterms.bibliographicCitation.volume
100
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
DEAL Wiley
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34482537
dcterms.isPartOf.issn
0009-9163
dcterms.isPartOf.eissn
1399-0004