{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:50:40Z","timestamp":1792144240176,"version":"4.4.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"TUBITAK","award":["216S771"],"award-info":[{"award-number":["216S771"]}]},{"DOI":"10.13039\/501100004412","name":"Turkish Academy of Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004412","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["212219\/Z\/18\/Z"],"award-info":[{"award-number":["212219\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council Mitochondrial Biology Unit","award":["MC_UU_00015\/9"],"award-info":[{"award-number":["MC_UU_00015\/9"]}]},{"DOI":"10.13039\/501100000275","name":"Leverhulme Trust","doi-asserted-by":"publisher","award":["RPG-2018\u2013408"],"award-info":[{"award-number":["RPG-2018\u2013408"]}],"id":[{"id":"10.13039\/501100000275","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC","award":["MR\/S035699\/1"],"award-info":[{"award-number":["MR\/S035699\/1"]}]},{"DOI":"10.13039\/501100017506","name":"Alzheimer\u2019s Society","doi-asserted-by":"crossref","award":["AS-PG-18b-022"],"award-info":[{"award-number":["AS-PG-18b-022"]}],"id":[{"id":"10.13039\/501100017506","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["BRC-1215\u201320014"],"award-info":[{"award-number":["BRC-1215\u201320014"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000276","name":"Department of Health and Social Care","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["309548"],"award-info":[{"award-number":["309548"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Investigator Award","award":["109915\/Z\/15\/Z"],"award-info":[{"award-number":["109915\/Z\/15\/Z"]}]},{"name":"Medical Research Council","award":["MR\/N025431\/1"],"award-info":[{"award-number":["MR\/N025431\/1"]}]},{"name":"Wellcome Trust Pathfinder Scheme","award":["201064\/Z\/16\/Z"],"award-info":[{"award-number":["201064\/Z\/16\/Z"]}]},{"DOI":"10.13039\/100010897","name":"Newton Fund","doi-asserted-by":"publisher","award":["UK\/Turkey, MR\/N027302\/1"],"award-info":[{"award-number":["UK\/Turkey, MR\/N027302\/1"]}],"id":[{"id":"10.13039\/100010897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022186","name":"Lily Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022186","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Stoneygate Trust"},{"DOI":"10.13039\/501100004282","name":"Evelyn Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004282","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Addenbrookes Charitable Trust","award":["G100142"],"award-info":[{"award-number":["G100142"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN-167281"],"award-info":[{"award-number":["FDN-167281"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000223","name":"Muscular Dystrophy Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000223","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"crossref","award":["CFI-JELF 38412"],"award-info":[{"award-number":["CFI-JELF 38412"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"crossref","award":["950\u2013232279"],"award-info":[{"award-number":["950\u2013232279"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["UM1 HG008900"],"award-info":[{"award-number":["UM1 HG008900"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["R01 HG009141"],"award-info":[{"award-number":["R01 HG009141"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RD-Connect Genome-Phenome Analysis","award":["FP7\/2007\u20132013"],"award-info":[{"award-number":["FP7\/2007\u20132013"]}]},{"name":"RD-Connect Genome-Phenome Analysis","award":["n\u00b0 305444"],"award-info":[{"award-number":["n\u00b0 305444"]}]},{"name":"EJP-RD and INB\/ELIXIR-ES"},{"name":"Horizon 2020 research and innovation program","award":["779257"],"award-info":[{"award-number":["779257"]}]},{"name":"International Centre for Genomic Medicine in Neuromuscular Diseases","award":["MR\/S005021\/1"],"award-info":[{"award-number":["MR\/S005021\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Consanguineous marriages have a prevalence rate of 24% in Turkey. These carry an increased risk of autosomal recessive genetic conditions, leading to severe disability or premature death, with a significant health and economic burden. A definitive molecular diagnosis could not be achieved in these children previously, as infrastructures and access to sophisticated diagnostic options were limited. We studied the cause of neurogenetic disease in 246 children from 190 consanguineous families recruited in three Turkish hospitals between 2016 and 2020. All patients underwent deep phenotyping and trio whole exome sequencing, and data were integrated in advanced international bioinformatics platforms.<\/jats:p>\n               <jats:p>We detected causative variants in 119 known disease genes in 72% of families. Due to overlapping phenotypes 52% of the confirmed genetic diagnoses would have been missed on targeted diagnostic gene panels. Likely pathogenic variants in 27 novel genes in 14% of the families increased the diagnostic yield to 86%. Eighty-two per cent of causative variants (141\/172) were homozygous, 11 of which were detected in genes previously only associated with autosomal dominant inheritance. Eight families carried two pathogenic variants in different disease genes. De novo (9.3%), X-linked recessive (5.2%) and compound heterozygous (3.5%) variants were less frequent compared to non-consanguineous populations.<\/jats:p>\n               <jats:p>This cohort provided a unique opportunity to better understand the genetic characteristics of neurogenetic diseases in a consanguineous population. Contrary to what may be expected, causative variants were often not on the longest run of homozygosity and the diagnostic yield was lower in families with the highest degree of consanguinity, due to the high number of homozygous variants in these patients. Pathway analysis highlighted that protein synthesis\/degradation defects and metabolic diseases are the most common pathways underlying paediatric neurogenetic disease. In our cohort 164 families (86%) received a diagnosis, enabling prevention of transmission and targeted treatments in 24 patients (10%).<\/jats:p>\n               <jats:p>We generated an important body of genomic data with lasting impacts on the health and wellbeing of consanguineous families and economic benefit for the healthcare system in Turkey and elsewhere. We demonstrate that an untargeted next generation sequencing approach is far superior to a more targeted gene panel approach, and can be performed without specialized bioinformatics knowledge by clinicians using established pipelines in populations with high rates of consanguinity.<\/jats:p>","DOI":"10.1093\/brain\/awab395","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T18:45:47Z","timestamp":1634150747000},"page":"1507-1518","source":"Crossref","is-referenced-by-count":37,"title":["High diagnostic rate of trio exome sequencing in consanguineous families with neurogenetic diseases"],"prefix":"10.1093","volume":"145","author":[{"given":"Semra","family":"Hiz Kurul","sequence":"first","affiliation":[{"name":"Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir 35340, Turkey"},{"name":"Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey"},{"name":"Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yavuz","family":"Oktay","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir 35340, Turkey"},{"name":"Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey"},{"name":"Department of Medical Biology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"T\u00f6pf","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, Institute of Translational and Clinical Research, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00f3ra Zs","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Epilepsy-Neurology Polyclinic of Buda Children's Hospital, New Saint John's Hospital and Northern -Buda United Hospitals, Budapest 1023, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdal","family":"G\u00fcng\u00f6r","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Faculty of Medicine, Turgut Ozal Research Center, Inonu University, Malatya 44210, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Yaramis","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Clinic, Diyarbakir 21070, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ece","family":"Sonmezler","sequence":"additional","affiliation":[{"name":"Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Matalonga","sequence":"additional","affiliation":[{"name":"CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona 08003, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uluc","family":"Yis","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Schon","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK"},{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Paramonov","sequence":"additional","affiliation":[{"name":"CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona 08003, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130pek Polat","family":"Kalafatcilar","sequence":"additional","affiliation":[{"name":"Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey"},{"name":"Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK"},{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliz","family":"Rieger","sequence":"additional","affiliation":[{"name":"Rehabilitation Centre for the Physically Handicapped, Budapest 1528, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur","family":"Arslan","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir 35340, Turkey"},{"name":"Department of Paediatric Nutrition and Metabolism, School of Medicine, Dokuz Eylul University, Izmir 1528, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmasnur","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcu","family":"Ekinci","sequence":"additional","affiliation":[{"name":"Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar Pulat","family":"Edem","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmut","family":"Aslan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Faculty of Medicine, Turgut Ozal Research Center, Inonu University, Malatya 44210, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilge","family":"\u00d6zg\u00f6r","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Faculty of Medicine, Turgut Ozal Research Center, Inonu University, Malatya 44210, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lochm\u00fcller","sequence":"additional","affiliation":[{"name":"GKT School of Medical Education, King's College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwati","family":"Nair","sequence":"additional","affiliation":[{"name":"GKT School of Medical Education, King's College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"O'Heir","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA SE1 1UL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alysia K","family":"Lovgren","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA SE1 1UL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Broad Center for Mendelian Genomics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Polavarapu","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa ON K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Roos","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa ON K1H 8L1, Canada"},{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften, ISAS e.V., Dortmund 44227, Germany"},{"name":"Department of Pediatric Neurology, University of Duisburg-Essen, Essen 45141, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane S","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK"},{"name":"Department of Clinical Neurosciences, John Van Geest Centre for Brain Repair, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0PY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa","family":"Hathazi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK"},{"name":"Department of Clinical Neurosciences, John Van Geest Centre for Brain Repair, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0PY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7065-6617","authenticated-orcid":false,"given":"Patrick F","family":"Chinnery","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK"},{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Laurie","sequence":"additional","affiliation":[{"name":"CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona 08003, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Beltran","sequence":"additional","affiliation":[{"name":"CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona 08003, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanns","family":"Lochm\u00fcller","sequence":"additional","affiliation":[{"name":"CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona 08003, Spain"},{"name":"Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa ON K1H 8L1, Canada"},{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany"},{"name":"Division of Neurology, Department of Medicine, The Ottawa Hospital; and Brain and Mind Research Institute, University of Ottawa, Ottawa ON K1Y 4E9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-170X","authenticated-orcid":false,"given":"Rita","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK"},{"name":"Department of Clinical Neurosciences, John Van Geest Centre for Brain Repair, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0PY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"issue":"2","key":"2022052416104594400_awab395-B1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/03014460.2016.1265148","article-title":"Genetics of consanguinity and inbreeding in health and disease","volume":"44","author":"Fareed","year":"2017","journal-title":"Ann Hum Biol"},{"issue":"4","key":"2022052416104594400_awab395-B2","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1017\/S0021932016000742","article-title":"The causal relationship between consanguineous marriages and infant mortality in Turkey","volume":"49","author":"Ko\u00e7","year":"2017","journal-title":"J Biosoc Sci"},{"issue":"6","key":"2022052416104594400_awab395-B3","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s00439-013-1286-3","article-title":"Hunting human disease genes: Lessons from the past, challenges for the future","volume":"132","author":"Brunham","year":"2013","journal-title":"Hum Genet"},{"issue":"6","key":"2022052416104594400_awab395-B4","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1007\/s10897-013-9644-9","article-title":"Genetic screening services provided in Turkey","volume":"22","author":"Erdem","year":"2013","journal-title":"J Genet Couns"},{"issue":"3","key":"2022052416104594400_awab395-B5","first-page":"207","article-title":"The frequency of consanguineous marriage in eastern Turkey","volume":"20","author":"Akbayram","year":"2009","journal-title":"Genet Couns"},{"issue":"2","key":"2022052416104594400_awab395-B6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1034\/j.1399-0004.2001.600201.x","article-title":"Consanguinity and its relevance to clinical genetics","volume":"60","author":"Bittles","year":"2001","journal-title":"Clin Genet"},{"issue":"1","key":"2022052416104594400_awab395-B7","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1468-1331.2011.03590.x","article-title":"The economic cost of brain disorders in Europe","volume":"19","author":"Olesen","year":"2012","journal-title":"Eur J Neurol"},{"issue":"5","key":"2022052416104594400_awab395-B8","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ajhg.2017.04.003","article-title":"International cooperation to enable the diagnosis of all rare genetic diseases","volume":"100","author":"Boycott","year":"2017","journal-title":"Am J Hum Genet"},{"issue":"3","key":"2022052416104594400_awab395-B9","doi-asserted-by":"crossref","first-page":"404","DOI":"10.2174\/0929867324666170718101946","article-title":"NGS technologies as a turning point in rare disease research, diagnosis and treatment","volume":"25","author":"Fernandez-Marmiesse","year":"2018","journal-title":"Curr Med Chem"},{"issue":"5","key":"2022052416104594400_awab395-B10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"21","key":"2022052416104594400_awab395-B11","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1093\/bioinformatics\/btu483","article-title":"MToolBox: A highly automated pipeline for heteroplasmy annotation and prioritization analysis of human mitochondrial variants in high-throughput sequencing","volume":"30","author":"Calabrese","year":"2014","journal-title":"Bioinformatics"},{"issue":"3","key":"2022052416104594400_awab395-B12","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"6","key":"2022052416104594400_awab395-B13","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/gim.2015.139","article-title":"Novel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing","volume":"18","author":"Kancheva","year":"2016","journal-title":"Genet Med"},{"issue":"Suppl 1","key":"2022052416104594400_awab395-B14","first-page":"642","article-title":"Automated re-analysis of over 7,500 exomes and genomes within Solve-RD demonstrates its power to deliver diagnosis for rare disease patients","volume":"28","author":"Matalonga","year":"2020","journal-title":"Eur J Hum Genet"},{"issue":"6","key":"2022052416104594400_awab395-B15","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S1474-4422(20)30028-4","article-title":"Advances in the diagnosis of inherited neuromuscular diseases and implications for therapy development","volume":"19","author":"Thompson","year":"2020","journal-title":"Lancet Neurol"},{"issue":"1","key":"2022052416104594400_awab395-B16","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1001\/jama.2014.7184","article-title":"Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies","volume":"312","author":"Taylor","year":"2014","journal-title":"Jama"},{"issue":"5","key":"2022052416104594400_awab395-B17","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/s41431-019-0552-9","article-title":"A de novo variant in the human HIST1H4J gene causes a syndrome analogous to the HIST1H4C-associated neurodevelopmental disorder","volume":"28","author":"Tessadori","year":"2020","journal-title":"Eur J Hum Genet"},{"issue":"5","key":"2022052416104594400_awab395-B18","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s10038-019-0570-z","article-title":"Biallelic loss of EEF1D function links heat shock response pathway to autosomal recessive intellectual disability","volume":"64","author":"Ugur Iseri","year":"2019","journal-title":"J Hum Genet"},{"key":"2022052416104594400_awab395-B19","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41525-019-0098-3","article-title":"A large data resource of genomic copy number variation across neurodevelopmental disorders","volume":"4","author":"Zarrei","year":"2019","journal-title":"NPJ Genom Med"},{"issue":"3","key":"2022052416104594400_awab395-B20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.neuron.2015.09.048","article-title":"Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease","volume":"88","author":"Karaca","year":"2015","journal-title":"Neuron"},{"issue":"10","key":"2022052416104594400_awab395-B21","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1083\/jcb.201705151","article-title":"WDR91 is a Rab7 effector required for neuronal development","volume":"216","author":"Liu","year":"2017","journal-title":"J Cell Biol"},{"issue":"5","key":"2022052416104594400_awab395-B22","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/s41436-020-01071-z","article-title":"A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy","volume":"23","author":"Ni","year":"2021","journal-title":"Genet Med"},{"issue":"9","key":"2022052416104594400_awab395-B23","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/gim.2017.1","article-title":"A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology","volume":"19","author":"Vissers","year":"2017","journal-title":"Genet Med"},{"issue":"7642","key":"2022052416104594400_awab395-B24","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nature21062","article-title":"Prevalence and architecture of de novo mutations in developmental disorders","volume":"542","author":"Deciphering Developmental Disorders Study","year":"2017","journal-title":"Nature"},{"issue":"7814","key":"2022052416104594400_awab395-B25","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41586-020-2434-2","article-title":"Whole-genome sequencing of patients with rare diseases in a national health system","volume":"583","author":"Turro","year":"2020","journal-title":"Nature"},{"issue":"7","key":"2022052416104594400_awab395-B26","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/ng.390","article-title":"Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome","volume":"41","author":"Weraarpachai","year":"2009","journal-title":"Nat Genet"},{"issue":"6","key":"2022052416104594400_awab395-B27","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ng.378","article-title":"SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy","volume":"41","author":"Ghezzi","year":"2009","journal-title":"Nat Genet"},{"issue":"2","key":"2022052416104594400_awab395-B28","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/ng.3469","article-title":"Timing, rates and spectra of human germline mutation","volume":"48","author":"Rahbari","year":"2016","journal-title":"Nat Genet"},{"issue":"11","key":"2022052416104594400_awab395-B29","doi-asserted-by":"crossref","first-page":"e00091","DOI":"10.1128\/MRA.00091-21","article-title":"Draft genome sequence of a Burkholderia epacian complex strain isolated from a human intra-abdominal abscess","volume":"10","author":"Zhai","year":"2021","journal-title":"Microbiol Resour Announc"},{"issue":"5","key":"2022052416104594400_awab395-B30","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/ana.24362","article-title":"Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease","volume":"77","author":"Gorman","year":"2015","journal-title":"Ann Neurol"},{"issue":"3","key":"2022052416104594400_awab395-B31","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41431-020-00756-y","article-title":"Parental exome analysis identifies shared carrier status for a second recessive disorder in couples with an affected child","volume":"29","author":"Mor-Shaked","year":"2020","journal-title":"Eur J Hum Genet"},{"issue":"5","key":"2022052416104594400_awab395-B32","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/s41431-018-0099-1","article-title":"Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders","volume":"26","author":"Dillon","year":"2018","journal-title":"Eur J Hum Genet"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awab395\/43293503\/awab395.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/145\/4\/1507\/43811762\/awab395.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/145\/4\/1507\/43811762\/awab395.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T16:12:16Z","timestamp":1653408736000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/145\/4\/1507\/6430107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,11,17]]},"published-print":{"date-parts":[[2022,5,24]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awab395","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,1]]},"published":{"date-parts":[[2021,11,17]]}}}