biostudies-literaturePagnamenta ATNIH National Institute of Neurological Disorders and StrokeMDUKSwedish Research CouncilCMMC fellowshipNHS EnglandSidra Medicine Internal Research FundCancer Research UK and the Medical Research CouncilDeutsche ForschungsgemeinschaftMRC and the Biomedical Research Centres at UCL and UCLHMedical Research CouncilEuropean Union’s Seventh Framework Programme for researchNational Institute for Health Research (NIHR)NIHR Biomedical Research Centre OxfordMuscular Dystrophy UKMRC, AtaxiaWellcome TrustNational Health Service as part of their care and support584-600https://www.ebi.ac.uk/biostudies/studies/S-EPMC8263055biostudies-literatureUnknown144(2)The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length Brain : a journal of neurologyAn ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy.PMC8263055MR/M009203/1Wi 945/19-1MC_PC_14089Wi 945/18-1NF-SI-0515-10022NF-SI-0617-10154RA4/0924MR/T001712/1HDR-9004MR/S006753/1203141/Z/16/ZMC_EX_MR/M009203/160847318GRO-PG24-0271IRF-2019, SDR400034CMMC C18Stevens HETaylor JCCortese ACraig CEHChan GCWilliams EBonnemann CGSultana RSmith KRBoissiere JMMaroofian RWalsh EMaleady-Crowe FLahnstein LHubbard TJPFoley ARWelland MJMuraresku CCStuckey AGutowski NZarowiecki MCaulfield MJHamblin AMueller MO'Donovan POrioli ADonkervoort SAmbrose JCScott RHSpooner WSarkozy AMcDonagh EMTucci ADa'as SIBleda MLeigh SEAPatch CThomas ERAJones LJMason JArumugam PRiesgo-Ferreiro PHenderson SPolychronopoulos DDominik NLawson KTajsharghi HHalai DMurugaesu NLeong IUSKousathanas AWitkowska KJungbluth HTanguy MSmith SCGiess ARendon ALauffer MPerez-Gil DBoustred CRSiddiq ARankin JOdhams CAYip JDevereau AWood SMMedne LO'Driscoll MSavage KNeuhaus SBFowler TKaiyrzhanov RDaugherty LCTregidgo CPullinger JBasiri KFerla MPLavin TFakhro KAAnsari BFernandez-Garcia MAGenomics England Research ConsortiumHoulden HWatters SABarresi RNemeth AHWunderlich GBurca AElgar GHolman JESieghart AYum SWWirth BSedghi MReilly MMBrusius IMoutsianas LBrittain HKasperaviciute DRyten MMarcelis CHackett JMPereira MBRogers TBoardman-Pretty FLassche SZou YBaple ELKayikci MThompson SRIbanez KMillan FMoslemi ARSmedley DPagnamenta ATFurio-Tari PNorwood FJackson RMarks PLopez JFKarakaya MSosinsky AMuntoni FFoulger RENeed ACSawant KBeetz CMarini-Bettolo CO'Donnell MZolkipli-Cunningham ZRahim TfalseAn ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy.The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length 2021-01-01T00:00:00Z2021 Mar2026-06-11T03:21:11.214Z2022-02-10T18:48:09.112ZS-EPMC82630553355968110.1093/brain/awaa420