Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis

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dc.contributor.authorAltunoglu, Umut
dc.contributor.authorPalencia-Campos, Adrian
dc.contributor.authorGuenes, Nilay
dc.contributor.authorTurgut, Gozde Tutku
dc.contributor.authorNevado, Julian
dc.contributor.authorLapunzina, Pablo
dc.contributor.authorValencia, Maria
dc.date.accessioned2024-04-24T17:11:59Z
dc.date.available2024-04-24T17:11:59Z
dc.date.issued2024
dc.departmentDicle Üniversitesien_US
dc.description.abstractBackground Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2. Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum.Methods We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays.Main results We identified pathogenic variants in EVC/EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3, respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated 'classical EvC findings' in the literature and highlighted findings previously undescribed or rarely described as part of EvC.Conclusions This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC/EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes.en_US
dc.description.sponsorshipSpanish Ministry of Economy and Competitiveness [SAF2010- 17901, SAF2013- 43365- R, SAF2016- 75434- R, PID2019- 105620RB- I00/AEI/10.13039/501100011033]; FEDER funds through ISCIII grant [PI20/01053, PMP21/00063]en_US
dc.description.sponsorshipThis work was funded by the Spanish Ministry of Economy and Competitiveness (SAF2010- 17901, SAF2013- 43365- R, SAF2016- 75434- R, PID2019- 105620RB- I00/AEI/10.13039/501100011033) and FEDER funds through ISCIII grant PI20/01053 and PMP21/00063/Instituto de Salud Carlos II.en_US
dc.identifier.doi10.1136/jmg-2023-109546
dc.identifier.issn0022-2593
dc.identifier.issn1468-6244
dc.identifier.pmid38531627
dc.identifier.scopus2-s2.0-85190121823
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1136/jmg-2023-109546
dc.identifier.urihttps://hdl.handle.net/11468/17806
dc.identifier.wosWOS:001191866100001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherBmj Publishing Groupen_US
dc.relation.ispartofJournal of Medical Genetics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCongenital, Hereditary, And Neonatal Diseases And Abnormalitiesen_US
dc.subjectHuman Geneticsen_US
dc.subjectMolecular Medicineen_US
dc.subjectPediatricsen_US
dc.titleVariant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosisen_US
dc.titleVariant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis
dc.typeArticleen_US

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