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dc.contributor.authorBaptista, Julia
dc.date.accessioned2023-04-20T16:36:34Z
dc.date.available2023-04-20T16:36:34Z
dc.date.issued2023-04-12
dc.identifier.issn1769-7212
dc.identifier.issn1878-0849
dc.identifier.other104768
dc.identifier.urihttps://pearl.plymouth.ac.uk/handle/10026.1/20739
dc.description.abstract

A de novo novel variant of uncertain significance p. (Arg532del) in the KLHL15 gene was identified by trio exome analysis in a child with global developmental delay, coarse facial features, repetitive behaviour, increased fatigability, poor feeding and gastro-oesophageal reflux. Comparative modelling and structural analysis were performed to gain insight into the effects of the variant on KLHL15 protein structure and function, with a view to aiding variant classification. The p. (Arg532del) variant affects a highly conserved residue within one of the Kelch repeats of the KLHL15 protein. This residue contributes to the stability of loop regions at the substrate binding surface of the protein; comparative modelling of the variant protein predicts altered topology at this surface, including at residue Tyr552, which is known to be important for substrate binding. We propose that it is highly probable that the p. (Arg532del) variant has a deleterious impact on KLHL15 structure, leading to a reduced level of protein function in vivo.

dc.format.extent104768-104768
dc.format.mediumPrint-Electronic
dc.languageen
dc.publisherElsevier
dc.subjectKLHL15
dc.subjectStructural analysis
dc.subjectProtein function
dc.subjectVariant classification
dc.titleClinical findings and structural analysis involving a patient with a novel KLHL15 variant
dc.typejournal-article
dc.typeCase Reports
dc.typeJournal Article
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:001053666300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue6
plymouth.volume66
plymouth.publication-statusPublished
plymouth.journalEuropean Journal of Medical Genetics
dc.identifier.doi10.1016/j.ejmg.2023.104768
plymouth.organisational-group|Plymouth
plymouth.organisational-group|Plymouth|Faculty of Health
plymouth.organisational-group|Plymouth|Users by role
plymouth.organisational-group|Plymouth|Users by role|Academics
plymouth.organisational-group|Plymouth|Faculty of Health|Peninsula Medical School
dc.publisher.placeNetherlands
dcterms.dateAccepted2023-04-12
dc.date.updated2023-04-20T16:36:34Z
dc.rights.embargodate2024-4-12
dc.identifier.eissn1878-0849
dc.rights.embargoperiodforever
rioxxterms.versionofrecord10.1016/j.ejmg.2023.104768


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