biostudies-literatureIbanez KRosetrees TrustMedical Research CouncilNational Institute for Health Research (NIHR)Alzheimer's SocietyWellcome TrustParkinson's UK234-245https://www.ebi.ac.uk/biostudies/studies/S-EPMC8850201biostudies-literatureUnknown21(3)<h4>Background</h4>Repeat expansion disorders affect about 1 in 3000 individuals and are clinically heterogeneous diseases caused by expansions of short tandem DNA repeats. Genetic testing is often locus-specific, resulting in underdiagnosis of people who have atypical clinical presentations, especially in paediatric patients without a previous positive family history. Whole genome sequencing is increasingly used as a first-line test for other rare genetic disorders, and we aimed to assess its performance in the diagnosis of patients with neurological repeat expansion disorders.<h4>Methods</h4>We retrospectively assessed the diagnostic accuracy of whole genome sequencing to detect the most common repeat expansion loci associated with neurological outcomes (AR, ATN1, ATXN1, ATXN2, ATXN3, ATThe Lancet. NeurologyWhole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study.PMC8850201G1001253MR/M009203/1MR/S01165X/1MR/K000608/1MC_PC_14089MR/L501542/1MR/K01417X/1NF-SI-0617-10154M733G0701075PGL19-2 1011817/90/01G-0907MR/S006753/1UKDRI-1009022212219/Z/18/ZMC_EX_MR/M009203/1NF-SI-0513-10141G-1307NF-SI-0512-10113MR/J004758/1G0901254Stevens HESchott JMTaylor JCCraig CEHWilliams EDouglas ASultana RVenkata LSmith KRWood NWBoissiere JMWalsh EHackett JMaleady-Crowe FLahnstein LPerry DLHubbard TJPWGS for Neurological Diseases GroupChan GLabrum RWelland MJTemple IKStuckey AChinnery PFZarowiecki MCaulfield MJTwiss PPolke JHamblin AFaravelli FMueller MRosser EScott RHAmbrose JCSpooner WMcDonagh EMFestenstein RTucci AVandrovcova JNewman WBleda MThomas ERAPatch CLeigh SEASheikh IJones LJMason JArumugam PRiesgo-Ferreiro PHenderson SRaymond FLPolychronopoulos DSantos LHoward RLawson KHalai DMurugaesu NLeong IUSHolman JWitkowska KBourn DDolzhenko ERendon APerez-Gil DDeshpande VBoustred CRde Burca AWilson GSiddiq AAjay SSAbbs SOdhams CAWarner TTDevereau AWood SMHill SSavage KAngus-Leppan HTaylor Tavares ALFowler TDaugherty LCNeed ATregidgo CPullinger JHyder ZEberle MAFlinter FALaura MGreenhalgh LGenomics England Research ConsortiumHagelstrom RTEggleton KHoulden HWatters SABrennan PNaresh KElgar GSieghart AAlmheiri GDavison JEBhatia KPSchrag AReilly MMTaft RJMenzies LMoutsianas LHardy JBrittain HKasperaviciute DEllard SRyten MFratta PRogers TGiunti PBoardman-Pretty FOprych KChitty LSMcEntagart MRajan VKayikci MThompson SRIbanez KMorris HSmedley DMcMullan DRueda AMumford ASayer JAFurio-Tari PJackson RLopez JFDeans ZCRobinson RSosinsky AChawla AFoulger RESawant KBaple EPasko DRahim TfalseWhole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study.<h4>Background</h4>Repeat expansion disorders affect about 1 in 3000 individuals and are clinically heterogeneous diseases caused by expansions of short tandem DNA repeats. Genetic testing is often locus-specific, resulting in underdiagnosis of people who have atypical clinical presentations, especially in paediatric patients without a previous positive family history. Whole genome sequencing is increasingly used as a first-line test for other rare genetic disorders, and we aimed to assess its performance in the diagnosis of patients with neurological repeat expansion disorders.<h4>Methods</h4>We retrospectively assessed the diagnostic accuracy of whole genome sequencing to detect the most common repeat expansion loci associated with neurological outcomes (AR, ATN1, ATXN1, ATXN2, ATXN3, AT2022-01-01T00:00:00Z2022 Mar2025-04-04T19:43:19.939Z2022-07-19T07:11:28.447ZS-EPMC88502013518250910.1016/S1474-4422(21)00462-2