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dc.contributor.authorJurkute, Neringa
dc.contributor.authorD'Esposito, Fabiana
dc.contributor.authorRobson, Anthony G
dc.contributor.authorPitceathly, Robert DS
dc.contributor.authorCordeiro, Francesca
dc.contributor.authorRaymond, F Lucy
dc.contributor.authorMoore, Anthony T
dc.contributor.authorMichaelides, Michel
dc.contributor.authorYu-Wai-Man, Patrick
dc.contributor.authorWebster, Andrew R
dc.contributor.authorArno, Gavin
dc.contributor.authorGenomics England Research Consortium
dc.date.accessioned2022-01-28T16:43:24Z
dc.date.available2022-01-28T16:43:24Z
dc.date.issued2021-12-01
dc.identifier.issn0146-0404
dc.identifier.other34905022
dc.identifier.otherPMC8684315
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333270
dc.descriptionFunder: Wellcome Trust
dc.description.abstractPURPOSE: To report novel genotypes and expand the phenotype spectrum of SSBP1-disease and explore potential disease mechanism. METHODS: Five families with previously unsolved optic atrophy and retinal dystrophy underwent whole genome sequencing as part of the National Institute for Health Research BioResource Rare-Diseases and the UK's 100,000 Genomes Project. In silico analysis and protein modelling was performed on the identified variants. Deep phenotyping including retinal imaging and International Society for Clinical Electrophysiology of Vision standard visual electrophysiology was performed. RESULTS: Seven individuals from five unrelated families with bilateral optic atrophy and/or retinal dystrophy with extraocular signs and symptoms in some are described. In total, 6 SSBP1 variants were identified including the previously unreported variants: c.151A>G, p.(Lys51Glu), c.335G>A p.(Gly112Glu), and c.380G>A, p.(Arg127Gln). One individual was found to carry biallelic variants (c.380G>A p.(Arg127Gln); c.394A>G p.(Ile132Val)) associated with likely autosomal recessive SSBP1-disease. In silico analysis predicted all variants to be pathogenic and Three-dimensional protein modelling suggested possible disease mechanisms via decreased single-stranded DNA binding affinity or impaired higher structure formation. CONCLUSIONS: SSBP1 is essential for mitochondrial DNA replication and maintenance, with defects leading to a spectrum of disease that includes optic atrophy and/or retinal dystrophy, occurring with or without extraocular features. This study provides evidence of intrafamilial variability and confirms the existence of an autosomal recessive inheritance in SSBP1-disease consequent upon a previously unreported genotype.
dc.languageeng
dc.publisherAssociation for Research in Vision and Ophthalmology (ARVO)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 7703701
dc.sourceessn: 1552-5783
dc.subjectHumans
dc.subjectOptic Atrophy
dc.subjectMitochondrial Diseases
dc.subjectDNA-Binding Proteins
dc.subjectMitochondrial Proteins
dc.subjectDNA, Mitochondrial
dc.subjectElectroretinography
dc.subjectPedigree
dc.subjectAmino Acid Sequence
dc.subjectMolecular Conformation
dc.subjectProtein Structure, Quaternary
dc.subjectGenes, Recessive
dc.subjectPenetrance
dc.subjectMutation, Missense
dc.subjectMolecular Sequence Data
dc.subjectAdolescent
dc.subjectMiddle Aged
dc.subjectChild, Preschool
dc.subjectFemale
dc.subjectMale
dc.subjectProtein Stability
dc.subjectRetinal Dystrophies
dc.subjectGenotyping Techniques
dc.subjectWhole Genome Sequencing
dc.titleSSBP1-Disease Update: Expanding the Genetic and Clinical Spectrum, Reporting Variable Penetrance and Confirming Recessive Inheritance.
dc.typeArticle
dc.date.updated2022-01-28T16:43:22Z
prism.issueIdentifier15
prism.publicationNameInvest Ophthalmol Vis Sci
prism.volume62
dc.identifier.doi10.17863/CAM.80693
rioxxterms.versionofrecord10.1167/iovs.62.15.12
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidYu Wai Man, Patrick [0000-0001-7847-9320]
dc.identifier.eissn1552-5783
pubs.funder-project-idNational Institute for Health Research (IS-BRC-1215-20014)
cam.issuedOnline2021-12-14


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International