Setleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutation

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dc.contributor.authorRosti, R. O.
dc.contributor.authorUyguner, Z. O.
dc.contributor.authorNazarenko, I.
dc.contributor.authorBekerecioglu, M.
dc.contributor.authorCadilla, C. L.
dc.contributor.authorOzgur, H.
dc.contributor.authorLee, B. H.
dc.date.accessioned2024-02-23T14:24:03Z
dc.date.available2024-02-23T14:24:03Z
dc.date.issued2015
dc.departmentNEÜen_US
dc.description.abstractSetleis syndrome is characterized by bitemporal scar-like lesions and other characteristic facial features. It results from recessive mutations that truncate critical functional domains in the basic helix-loop-helix (bHLH) transcription factor, TWIST2, which regulates expression of genes for facial development. To date, only four nonsense or small deletion mutations have been reported. In the current report, the clinical findings in a consanguineous Turkish family were characterized. Three affected siblings had the characteristic features of Setleis syndrome. Homozygosity for the first TWIST2 missense mutation, c.326T>C (p.Leu109Pro), was identified in the patients. In silico analyses predicted that the secondary structure of the mutant protein was sustained, but the empirical force field energy increased to an unfavorable level with the proline substitution (p.Leu109Pro). On a crystallographically generated dimer, p.Leu109 lies near the dimer interface, and the proline substitution is predicted to hinder dimer formation. Therefore, p.Leu109Pro-TWIST2 alters the three dimensional structure and is unable to dimerize, thereby hindering the binding of TWIST2 to its target genes involved in facial development.en_US
dc.description.sponsorshipCRANIRARE Project (TUBITAK-SBAG-ERANET) [112S398]en_US
dc.description.sponsorshipWe are grateful to the family members for their participation in this study. The molecular part of this work was supported by CRANIRARE Project (TUBITAK-SBAG-ERANET, 112S398).en_US
dc.identifier.doi10.1111/cge.12539
dc.identifier.endpage493en_US
dc.identifier.issn0009-9163
dc.identifier.issn1399-0004
dc.identifier.issue5en_US
dc.identifier.pmid25410422en_US
dc.identifier.scopus2-s2.0-84943352869en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage489en_US
dc.identifier.urihttps://doi.org/10.1111/cge.12539
dc.identifier.urihttps://hdl.handle.net/20.500.12452/13797
dc.identifier.volume88en_US
dc.identifier.wosWOS:000362682200013en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofClinical Geneticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectBhlh Domainen_US
dc.subjectFacial Developmenten_US
dc.subjectInborn Error Of Developmenten_US
dc.subjectMissense Mutationen_US
dc.subjectMolecular Modelingen_US
dc.subjectSetleis Syndromeen_US
dc.subjectTwist2en_US
dc.titleSetleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutationen_US
dc.typeArticleen_US

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