ArticleAmerican journal of human genetics2021
Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss.
Open access · bronzeAbstract readCase Reports
In one paragraph
Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- AFG2A-related encephalopathy, expanding the neurodevelopmental and epileptic spectrum.Orphanet journal of rare diseases · 2026Pooled it
- Article
- Telethon Undiagnosed Disease Program: Structured approach to solving rare childhood-onset genetic diseases.Genetics in medicine open · 2026Article
- Neurodevelopmental Disorder with Psychomotor Delay, Hearing Loss, and Spasticity Caused by Compound HeterozygousJournal of clinical medicine · 2025Article
- Efficacy of repetitive peripheral magnetic stimulation in managing spasticity of the triceps surae muscle in children with cerebral palsy: a retrospective analysis of influencing factors.BMC pediatrics · 2025Article
- Neurogenetic Disorders with Hearing Loss: Mechanisms, Classifications, and Emerging Insights.Current neurology and neuroscience reports · 2025Review
- A programmed decline in ribosome levels governs human early neurodevelopment.Nature cell biology · 2025Article
- Cryo-EM structure of the AAA+ SPATA5 complex and its role in human cytoplasmic pre-60S maturation.Nature communications · 2025Article
- Optimizing gRNA selection for high-penetrance F0 CRISPR screening for interrogating disease gene function.Nucleic acids research · 2025Article
- Elucidating the genomic basis of rare pediatric neurological diseases in Central Asia and Transcaucasia.Nature genetics · 2024Article
- Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings.Nature genetics · 2024Article
- Transcriptome-Wide Association Study Reveals New Molecular Interactions Associated with Melanoma Pathogenesis.Cancers · 2024Article
- Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome.Brain : a journal of neurology · 2024Article
- The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity.Cell · 2024Article
- Genetic and phenotypic analysis of 225 Chinese children with developmental delay and/or intellectual disability using whole-exome sequencing.BMC genomics · 2024Article
- Redefining cerebral palsies as a diverse group of neurodevelopmental disorders with genetic aetiology.Nature reviews. Neurology · 2023Review
- Ribosome biogenesis factors-from names to functions.The EMBO journal · 2023Review
- Ribosome biogenesis and function in development and disease.Development (Cambridge, England) · 2023Review
- The RD-Connect Genome-Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases.Human mutation · 2022Article
- Labeling of heterochronic ribosomes reveals C1ORF109 and SPATA5 control a late step in human ribosome assembly.Cell reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
105 authors at 20 institutions in 10 countries.
Elodie M RichardDepartment of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Somayeh BakhtiariBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Ashley P L MarshBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Rauan KaiyrzhanovDepartment of Neuromuscular Disorders, Institute of Neurology, University College London, Queen Square, WC1N 3BG London, UK.
Matias WagnerInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany; Institute of Neurogenomics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Sheetal ShettyBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Alex PagnozziCSIRO Health and Biosecurity, The Australian e-Health Research Centre, Brisbane, QLD 4029, Australia.
Sandra M NordlieBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Brandon S GuidaBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Patricia CornejoPediatric Neuroradiology Division, Pediatric Radiology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; University of Arizona College of Medicine, Phoenix, AZ 85004, USA; Mayo Clinic, Scottsdale, AZ 85259, USA.
Helen MageeBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
James LiuBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Bethany Y NortonBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Richard I WebsterNeurology Department, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
Lisa WorganDepartment of Medical Genomics, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
Hakon HakonarsonCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Jiankang LiDepartment of Computer Science, City University of Hong Kong, Kowloon 999077, Hong Kong.
Yiran GuoCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Center for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA.
Mahim JainDepartment of Bone and Osteogenesis Imperfecta, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Alyssa BlessonCenter for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, MD 21211, USA.
Lance H RodanDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.
Mary-Alice AbbottUniversity of Massachusetts Medical School - Baystate, Baystate Children's Hospital, Springfield, MA 01107, USA.
Anne ComiDepartment of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Julie S CohenDepartment of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Bader AlhaddadInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
Thomas MeitingerInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
Dominic LenzCentre of Child and Adolescent Medicine, Department of Pediatric Neurology and Metabolic Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Andreas ZieglerDepartment of Child Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Urania KotzaeridouDepartment of Child Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Theresa BrunetInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
Anna ChasseventDepartment of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Constance Smith-HicksDepartment of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Joseph EksteinDor Yeshorim, Committee for Prevention of Jewish Genetic Diseases, New York, NY 11211, USA.
Tzvi WeidenDor Yeshorim, Committee for Prevention of Jewish Genetic Diseases, Jerusalem 9054020, Israel.
Andreas HahnDepartment of Child Neurology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
Nazira ZharkinbekovaDepartment of Neurology, South Kazakhstan Medical Academy, Shymkent 160001, Kazakhstan.
Peter TurnpennyClinical Genetics, Royal Devon & Exeter NHS Foundation Trust, EX1 2ED Exeter, UK.
Arianna TucciClinical Pharmacology, William Harvey Research Institute, Charterhouse Square, School of Medicine and Dentistry Queen Mary University of London, London EC1M 6BQ, UK.
Melissa YeltonPenn State Health Children's Hospital, Hershey, PA 17033, USA.
Rita HorvathDepartment of Clinical Neurosciences, John Van Geest Cambridge Centre for Brain Repair, University of Cambridge School of Clinical Medicine, CB2 0PY Cambridge, UK.
Serdal GungorInonu University, Faculty of Medicine, Turgut Ozal Research Center, Department of Paediatric Neurology, 44280 Malatya, Turkey.
Semra HizIzmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, 35340 Izmir, Turkey; Department of Pediatric Neurology, Faculty of Medicine, Dokuz Eylul University, 35340 Izmir, Turkey.
Yavuz OktayIzmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, 35340 Izmir, Turkey; Department of Medical Biology, Faculty of Medicine, Dokuz Eylul University, 35220 Izmir, Turkey.
Hanns LochmullerChildren's Hospital of Eastern Ontario Research Institute; Division of Neurology, Department of Medicine, The Ottawa Hospital, and Brain and Mind Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Marcella ZollinoUniversità Cattolica Sacro Cuore, Facoltà di Medicina e Chirurgia, Dipartimento Scienze della Vita e Sanità Pubblica, 00168 Roma, Italy; Fondazione Policlinico A. Gemelli IRCCS, Sezione di Medicina Genomica, 00168 Roma, Italy.
Manuela MorleoTelethon Institute of Genetics and Medicine, 80078 Pozzuoli, Naples, Italy.
Giuseppe MarangiUniversità Cattolica Sacro Cuore, Facoltà di Medicina e Chirurgia, Dipartimento Scienze della Vita e Sanità Pubblica, 00168 Roma, Italy; Fondazione Policlinico A. Gemelli IRCCS, Sezione di Medicina Genomica, 00168 Roma, Italy.
Vincenzo NigroTelethon Institute of Genetics and Medicine, 80078 Pozzuoli, Naples, Italy; Department of Precision Medicine, University of Campania "Luigi Vanvitelli," 80138 Naples, Italy.
Annalaura TorellaTelethon Institute of Genetics and Medicine, 80078 Pozzuoli, Naples, Italy; Department of Precision Medicine, University of Campania "Luigi Vanvitelli," 80138 Naples, Italy.
Michele PinelliTelethon Institute of Genetics and Medicine, 80078 Pozzuoli, Naples, Italy.
Simona AmentaUniversità Cattolica Sacro Cuore, Facoltà di Medicina e Chirurgia, Dipartimento Scienze della Vita e Sanità Pubblica, 00168 Roma, Italy; Fondazione Policlinico A. Gemelli IRCCS, Sezione di Medicina Genomica, 00168 Roma, Italy.
Ralf A HusainDepartment of Neuropediatrics, Jena University Hospital, 07747 Jena, Germany.
Benita GrossmannInstitute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tuebingen, Germany.
Marion RappInstitute of Systems Motor Science, University of Lübeck, 23538 Lübeck, Germany.
Claudia SteenDepartment of Paediatric and Adolescent Medicine, St Joseph Hospital, 12101 Berlin, Germany.
Iris MarquardtUniversity Children's Hospital Oldenburg, Department of Neuropaediatric and Metabolic Diseases, 26133 Oldenburg, Germany.
Mona GrimmelInstitute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tuebingen, Germany.
Ute GrasshoffInstitute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tuebingen, Germany.
G Christoph KorenkeUniversity Children's Hospital Oldenburg, Department of Neuropaediatric and Metabolic Diseases, 26133 Oldenburg, Germany.
Marta Owczarek-LipskaHuman Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, 26129 Oldenburg, Germany; Junior Research Group, Genetics of Childhood Brain Malformations, Faculty VI-School of Medicine and Health Sciences, University of Oldenburg, 26129 Oldenburg, Germany.
John NeidhardtHuman Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, 26129 Oldenburg, Germany; Research Center Neurosensory Science, University of Oldenburg, 26129 Oldenburg, Germany.
Francesca Clementina RadioGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Cecilia ManciniGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Dianela Judith Claps SepulvedaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Kirsty McWalterGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Amber BegtrupGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Amy CrunkGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Maria J Guillen SacotoGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Richard PersonGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Rhonda E SchnurGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Maria Margherita MancardiUnit of Child Neuropsichiatry, Department of Clinical and Surgical Neurosciences and Rehabilitation, IRCCS Giannina Gaslini, Genoa 16147, Italy.
Florian KreuderAustralian Regenerative Medicine Institute, Monash University, Clayton, VIC 3168, Australia.
Pasquale StrianoPediatric Neurology and Muscular Diseases Unit, IRRCS Istituto Giannina Gaslini, 16148 Genoa, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16142 Genoa, Italy.
Federico ZaraDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16142 Genoa, Italy; Unit of Medical Genetics, IRRCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
Wendy K ChungDepartments of Pediatrics and Medicine, Columbia University, New York, NY 10032, USA.
Warren A MarksDepartment of Neurology, Cook Children's Medical Center, Fort Worth, TX 76104, USA; Department of Pediatrics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Clare L van EykRobinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5006, Australia; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
Dani L WebberRobinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5006, Australia; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
Mark A CorbettRobinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5006, Australia; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
Kelly HarperRobinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5006, Australia; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
Jesia G BerryRobinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5006, Australia; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
Alastair H MacLennanRobinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5006, Australia; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
Jozef GeczRobinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5006, Australia; Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia; South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
Marco TartagliaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Vincenzo SalpietroPediatric Neurology and Muscular Diseases Unit, IRRCS Istituto Giannina Gaslini, 16148 Genoa, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16142 Genoa, Italy.
John ChristodoulouBrain and Mitochondrial Research Group, Murdoch Children's Research Institute, Melbourne Department of Paediatrics, University of Melbourne, Melbourne, VIC 3052, Australia; Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW 2006, Australia.
Jan KaslinAustralian Regenerative Medicine Institute, Monash University, Clayton, VIC 3168, Australia.
Sergio Padilla-LopezBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Kaya BilguvarYale Center for Genome Analysis, Yale University, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Alexander MunchauInstitute of Systems Motor Science, University of Lübeck, 23538 Lübeck, Germany.
Zubair M AhmedDepartment of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA; Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Robert B HufnagelOphthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Michael C FaheyDepartment of Paediatrics, Monash University, Melbourne, VIC 3168, Australia.
Reza MaroofianDepartment of Neuromuscular Disorders, Institute of Neurology, University College London, Queen Square, WC1N 3BG London, UK.
Henry HouldenDepartment of Neuromuscular Disorders, Institute of Neurology, University College London, Queen Square, WC1N 3BG London, UK.
Heinrich StichtInstitute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Shrikant M ManeYale Center for Genome Analysis, Yale University, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Aboulfazl RadDepartment of Otolaryngology - Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
Barbara VonaDepartment of Otolaryngology - Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
Sheng Chih JinDepartment of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Tobias B HaackInstitute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tuebingen, Germany; Centre for Rare Diseases, University of Tübingen, 72074 Tuebingen, Germany.
Christine MakowskiDepartment of Paediatrics, Adolescent Medicine and Neonatology, Munich Clinic, Schwabing Hospital and Technical University of Munich, School of Medicine, 80804 Munich, Germany.
Yoel HirschDor Yeshorim, Committee for Prevention of Jewish Genetic Diseases, New York, NY 11211, USA.
Saima RiazuddinDepartment of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA; Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA. Electronic address: sriazuddin@som.umaryland.edu.
Michael C KruerBarrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ 85016, USA; Departments of Child Health, Neurology, Cellular, and Molecular Medicine and Program in Genetics, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA. Electronic address: kruerm@arizona.edu.
Barrow Neurological Institute · USKennedy Krieger Institute · USThe University of Adelaide · AUUniversity of Tübingen · DEBambino Gesù Children's Hospital · ITIstituto Giannina Gaslini · ITTUM Klinikum · DEHeidelberg University · DENational Hospital for Neurology and Neurosurgery · GBUniversità Cattolica del Sacro Cuore · ITUniversity of Maryland, Baltimore · USAustralian Regenerative Medicine Institute · AUCarl von Ossietzky Universität Oldenburg · DEChildren's Hospital of Philadelphia · USDokuz Eylül University · TRKlinikum Oldenburg · DETelethon Institute Of Genetics And Medicine · ITUniversity of Campania "Luigi Vanvitelli" · ITUniversity of Lübeck · DEYale University · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MWU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8MGenetics and Functional Studies of Autosomal Recessive Neurological DisordersR01NS107428 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI Saima Riazuddin · 2018 to 2026
$4.7MGenomic Insights into the Neurobiology of Cerebral PalsyR01NS106298 · NINDS · UNIVERSITY OF ARIZONA · PI KRUER, MICHAEL C · 2019 to 2023
$3.7MIntegrative Genomic Analysis of Congenital Heart DiseaseR00HL143036 · NHLBI · WASHINGTON UNIVERSITY · PI JIN, SHENG CHIH · 2020 to 2022
$730kIntegrative Genomic Analysis of Congenital Heart DiseaseK99HL143036 · NHLBI · ROCKEFELLER UNIVERSITY · PI JIN, SHENG CHIH · 2019 to 2019
$178kDepartment of HealthMedical Research Council G1000848Medical Research Council MR/N010035/1Medical Research Council MR/N025431/1Medical Research Council MR/N025431/2Medical Research Council MR/S006753/1Medical Research Council MR/V009346/1NCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR002345NHLBI NIH HHS K99 HL143036NHLBI NIH HHS R00 HL143036NINDS NIH HHS R01 NS106298NINDS NIH HHS R01 NS107428Wellcome TrustWellcome Trust WT093205 MAWellcome Trust WT104033AIA
Abstract
Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.
Indexed as
Genetic Predisposition to DiseaseGenetic VariationAdolescentAdultAllelesAnimalsATPases Associated with Diverse Cellular ActivitiesCerebral PalsyChild, PreschoolEpilepsyFemaleHearing LossHumansInfantInfant, NewbornIntellectual DisabilityATPases Associated with Diverse Cellular ActivitiesSPATA5 protein, humanAAA+ superfamilyATPasecerebral palsyepilepsyintellectual disabilitymovement disorderneurodevelopmental disordersensorineural hearing lossSPATA5L1
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.