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Biallelic variants in HECT E3 paralogs, HECTD4 and UBE3C, encoding ubiquitin ligases cause neurodevelopmental disorders that overlap with Angelman syndrome

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dc.contributor.authorGEÇKİNLİ, BİLGEN BİLGE
dc.contributor.authorsFaqeih E. A. , Alghamdi M. A. , Almahroos M. A. , Alharby E., Almuntashri M., Alshangiti A. M. , Clément P., Calame D. G. , Qebibo L., Burglen L., et al.
dc.date.accessioned2022-12-22T12:35:08Z
dc.date.available2022-12-22T12:35:08Z
dc.date.issued2022-01-01
dc.description.abstract© 2022 American College of Medical Genetics and GenomicsPurpose: Pathogenic variants in genes encoding ubiquitin E3 ligases are known to cause neurodevelopmental syndromes. Additional neurodevelopmental disorders associated with the other genes encoding E3 ligases are yet to be identified. Methods: Chromosomal analysis and exome sequencing were used to identify the genetic causes in 10 patients from 7 unrelated families with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. Results: In total, 4 patients were found to have 3 different homozygous loss-of-function (LoF) variants, and 3 patients had 4 compound heterozygous missense variants in the candidate E3 ligase gene, HECTD4, that were rare, absent from controls as homozygous, and predicted to be deleterious in silico. In 3 patients from 2 families with Angelman-like syndrome, paralog-directed candidate gene approach detected 2 LoF variants in the other candidate E3 ligase gene, UBE3C, a paralog of the Angelman syndrome E3 ligase gene, UBE3A. The RNA studies in 4 patients with LoF variants in HECTD4 and UBE3C provided evidence for the LoF effect. Conclusion: HECTD4 and UBE3C are novel biallelic rare disease genes, expand the association of the other HECT E3 ligase group with neurodevelopmental syndromes, and could explain some of the missing heritability in patients with a suggestive clinical diagnosis of Angelman syndrome.
dc.identifier.citationFaqeih E. A. , Alghamdi M. A. , Almahroos M. A. , Alharby E., Almuntashri M., Alshangiti A. M. , Clément P., Calame D. G. , Qebibo L., Burglen L., et al., "Biallelic variants in HECT E3 paralogs, HECTD4 and UBE3C, encoding ubiquitin ligases cause neurodevelopmental disorders that overlap with Angelman syndrome", Genetics in Medicine, 2022
dc.identifier.doi10.1016/j.gim.2022.10.006
dc.identifier.issn1098-3600
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85142523320&origin=inward
dc.identifier.urihttps://hdl.handle.net/11424/283824
dc.language.isoeng
dc.relation.ispartofGenetics in Medicine
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTıp
dc.subjectDahili Tıp Bilimleri
dc.subjectTıbbi Genetik
dc.subjectYaşam Bilimleri
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectSağlık Bilimleri
dc.subjectTemel Bilimler
dc.subjectMedicine
dc.subjectInternal Medicine Sciences
dc.subjectMedical Genetics
dc.subjectLife Sciences
dc.subjectMolecular Biology and Genetics
dc.subjectHealth Sciences
dc.subjectNatural Sciences
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectGENETİK VE KALITIM
dc.subjectLife Sciences (LIFE)
dc.subjectMOLECULAR BIOLOGY & GENETICS
dc.subjectGENETICS & HEREDITY
dc.subjectGenetik (klinik)
dc.subjectGenetics (clinical)
dc.subjectE3 ligase
dc.subjectHECTD4
dc.subjectIntellectual disability
dc.subjectNeurobehavioral differences
dc.subjectUBE3C
dc.titleBiallelic variants in HECT E3 paralogs, HECTD4 and UBE3C, encoding ubiquitin ligases cause neurodevelopmental disorders that overlap with Angelman syndrome
dc.typearticle
dspace.entity.typePublication
local.avesis.id62be0f56-1050-449f-95e6-de96d40520ed
local.indexed.atPUBMED
local.indexed.atSCOPUS
relation.isAuthorOfPublication5f812a34-2d87-4040-b76f-0b90c1c695ae
relation.isAuthorOfPublication.latestForDiscovery5f812a34-2d87-4040-b76f-0b90c1c695ae

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