{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:47:11Z","timestamp":1792068431548,"version":"4.4.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL121358"],"award-info":[{"award-number":["R01 HL121358"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL126729"],"award-info":[{"award-number":["R01 HL126729"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hubei Province\u2019s Innovative Team","award":["2017CFA014"],"award-info":[{"award-number":["2017CFA014"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31430047"],"award-info":[{"award-number":["31430047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>KCNMA1 encodes the large-conductance Ca2+- and voltage-activated K+ (BK) potassium channel \u03b1-subunit, and pathogenic gain-of-function variants in this gene have been associated with a dominant form of generalized epilepsy and paroxysmal dyskinesia. Here, we genetically and functionally characterize eight novel loss-of-function (LoF) variants of KCNMA1. Genome or exome sequencing and the participation in the international Matchmaker Exchange effort allowed for the identification of novel KCNMA1 variants. Patch clamping was used to assess functionality of mutant BK channels. The KCNMA1 variants p.(Ser351Tyr), p.(Gly356Arg), p.(Gly375Arg), p.(Asn449fs) and p.(Ile663Val) abolished the BK current, whereas p.(Cys413Tyr) and p.(Pro805Leu) reduced the BK current amplitude and shifted the activation curves toward positive potentials. The p.(Asp984Asn) variant reduced the current amplitude without affecting kinetics. A phenotypic analysis of the patients carrying the recurrent p.(Gly375Arg) de novo missense LoF variant revealed a novel syndromic neurodevelopmental disorder associated with severe developmental delay, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic dysmorphic features. Patients with other LoF variants presented with neurological and developmental symptoms including developmental delay, intellectual disability, ataxia, axial hypotonia, cerebral atrophy and speech delay\/apraxia\/dysarthria. Therefore, LoF KCNMA1 variants are associated with a new syndrome characterized by a broad spectrum of neurological phenotypes and developmental disorders. LoF variants of KCNMA1 cause a new syndrome distinctly different from gain-of-function variants in the same gene.<\/jats:p>","DOI":"10.1093\/hmg\/ddz117","type":"journal-article","created":{"date-parts":[[2019,5,25]],"date-time":"2019-05-25T15:10:23Z","timestamp":1558797023000},"page":"2937-2951","source":"Crossref","is-referenced-by-count":90,"title":["De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes"],"prefix":"10.1093","volume":"28","author":[{"given":"Lina","family":"Liang","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Moutton","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Inserm UMR 1231 GAD team, Genetics of Developmental Disorders, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, Dijon 21070, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A","family":"Schrier Vergano","sequence":"additional","affiliation":[{"name":"Medical Genetics and Metabolism, Children\u2019s Hospital of The King\u2019s Daughters, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Cogn\u00e9","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU de Nantes, Nantes 44093, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Saint-Martin","sequence":"additional","affiliation":[{"name":"Neurop\u00e9diatrie, Centre de R\u00e9f\u00e9rence des Epilepsies Rares, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg 67098, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C E","family":"Hurst","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushuang","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Bodamer","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Boston Children\u2019s Hospital\/Harvard Medical School, Boston, MA 02115, USA"},{"name":"The Broad Institute of Harvard and MIT, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Thevenon","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Inserm UMR 1231 GAD team, Genetics of Developmental Disorders, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, Dijon 21070, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina Y","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Boston Children\u2019s Hospital\/Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU de Nantes, Nantes 44093, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Gerard","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace, Laboratoires de Diagnostic G\u00e9n\u00e9tique, Unit\u00e9 de G\u00e9n\u00e9tique Mol\u00e9culaire, Nouvel H\u00f4pital Civil, Strasbourg 67000, Franc"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelaide","family":"Rega","sequence":"additional","affiliation":[{"name":"Pediatric Radiologist, D\u00e9partement de Radiologie et Imagerie Diagnostique et Th\u00e9rapeutique, CHU, Dijon 21079, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Nambot","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Inserm UMR 1231 GAD team, Genetics of Developmental Disorders, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, Dijon 21070, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphn\u00e9","family":"Lehalle","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Inserm UMR 1231 GAD team, Genetics of Developmental Disorders, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, Dijon 21070, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannis","family":"Duffourd","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Inserm UMR 1231 GAD team, Genetics of Developmental Disorders, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, Dijon 21070, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Thauvin-Robinet","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Inserm UMR 1231 GAD team, Genetics of Developmental Disorders, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, Dijon 21070, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Syndromes Malformatifs, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares, H\u00f4pital d'Enfants, Dijon 21079, France"},{"name":"Inserm UMR 1231 GAD team, Genetics of Developmental Disorders, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, Dijon 21070, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"B\u00e9zieau","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU de Nantes, Nantes 44093, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon S","family":"Dure","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neurology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C","family":"Helbling","sequence":"additional","affiliation":[{"name":"Clinical Services Laboratory, HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bick","sequence":"additional","affiliation":[{"name":"Clinical Services Laboratory, HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia M S","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam 3015, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Vitobello","sequence":"additional","affiliation":[{"name":"Inserm UMR 1231 GAD team, Genetics of Developmental Disorders, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, Dijon 21070, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing Kenneth","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P. R. China"},{"name":"Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA"},{"name":"Department of Genetics and Genome Science, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,15]]},"reference":[{"key":"2019091012135163300_ref1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/ng1585","article-title":"Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder","volume":"37","author":"Du","year":"2005","journal-title":"Nat. Genet."},{"key":"2019091012135163300_ref2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1152\/physrev.00001.2016","article-title":"Molecular determinants of BK channel functional diversity and functioning","volume":"97","author":"Latorre","year":"2017","journal-title":"Physiol. Rev."},{"key":"2019091012135163300_ref3","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fnmol.2018.00258","article-title":"Physiological roles and therapeutic potential of Ca2+ activated potassium channels in the nervous system","volume":"11","author":"Kshatri","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"2019091012135163300_ref4","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/307693a0","article-title":"Calcium-activated potassium channels and their role in secretion","volume":"307","author":"Petersen","year":"1984","journal-title":"Nature"},{"key":"2019091012135163300_ref5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1523\/JNEUROSCI.12-01-00297.1992","article-title":"Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassium channels","volume":"12","author":"Robitaille","year":"1992","journal-title":"J. Neurosci."},{"key":"2019091012135163300_ref6","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1098\/rspb.1990.0123","article-title":"Preferential expression of transient potassium current (IA) by 'short' hair cells of the chick's cochlea","volume":"242","author":"Murrow","year":"1990","journal-title":"Proc. Biol. Sci."},{"key":"2019091012135163300_ref7","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1126\/science.1373909","article-title":"Regulation of arterial tone by activation of calcium-dependent potassium channels","volume":"256","author":"Brayden","year":"1992","journal-title":"Science"},{"key":"2019091012135163300_ref8","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1152\/jn.1999.82.5.2171","article-title":"Two components of transducer adaptation in auditory hair cells","volume":"82","author":"Wu","year":"1999","journal-title":"J. Neurophysiol."},{"key":"2019091012135163300_ref9","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/jcp.24435","article-title":"BKCa and hEag1 channels regulate cell proliferation and differentiation in human bone marrow-derived mesenchymal stem cells","volume":"229","author":"Zhang","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"2019091012135163300_ref10","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.3390\/ijms19082442","article-title":"Cell cycle regulation by Ca2+-activated K+ (BK) channels modulators in SH-SY5Y neuroblastoma cells","volume":"19","author":"Maqoud","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2019091012135163300_ref11","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/s41431-017-0073-3","article-title":"De novo BK channel variant causes epilepsy by affecting voltage gating but not Ca2+ sensitivity","volume":"26","author":"Li","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"2019091012135163300_ref12","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1007\/s00439-016-1726-y","article-title":"Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures","volume":"135","author":"Tabarki","year":"2016","journal-title":"Hum. Genet."},{"key":"2019091012135163300_ref13","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/mds.26216","article-title":"De novo KCNMA1 mutations in children with early-onset paroxysmal dyskinesia and developmental delay","volume":"30","author":"Zhang","year":"2015","journal-title":"Mov. Disord."},{"key":"2019091012135163300_ref14","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: a matching tool for connecting investigators with an interest in the same gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Hum. Mutat."},{"key":"2019091012135163300_ref15","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.neubiorev.2014.02.015","article-title":"Intellectual disability and autism spectrum disorders: causal genes and molecular mechanisms","volume":"46","author":"Srivastava","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"2019091012135163300_ref16","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrn2148","article-title":"The action potential in mammalian central neurons","volume":"8","author":"Bean","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"2019091012135163300_ref17","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/nrn1992","article-title":"High-conductance potassium channels of the SLO family","volume":"7","author":"Salkoff","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"2019091012135163300_ref18","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1136\/jmedgenet-2016-104117","article-title":"A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family","volume":"54","author":"Sheereen","year":"2017","journal-title":"J. Med. Genet."},{"key":"2019091012135163300_ref19","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1212\/01.WNL.0000146196.01316.A2","article-title":"A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation","volume":"63","author":"Higgins","year":"2004","journal-title":"Neurology"},{"key":"2019091012135163300_ref20","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1111\/j.1471-4159.2005.03344.x","article-title":"Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain","volume":"94","author":"Jo","year":"2005","journal-title":"J. Neurochem."},{"key":"2019091012135163300_ref21","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s10048-008-0128-2","article-title":"Dysregulation of large-conductance Ca2+\u2212activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation","volume":"9","author":"Higgins","year":"2008","journal-title":"Neurogenetics"},{"key":"2019091012135163300_ref22","doi-asserted-by":"crossref","first-page":"530","DOI":"10.14348\/molcells.2016.0033","article-title":"BK knockout by TALEN-mediated gene targeting in osteoblasts: KCNMA1 determines the proliferation and differentiation of osteoblasts","volume":"39","author":"Hei","year":"2016","journal-title":"Mol. Cells"},{"key":"2019091012135163300_ref23","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.jep.2014.06.053","article-title":"Relaxant effect of flavonoid naringenin on contractile activity of rat colonic smooth muscle","volume":"155","author":"Yang","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"2019091012135163300_ref24","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1016\/j.bbamcr.2014.02.019","article-title":"KCa and Ca(2+) channels: the complex thought","volume":"1843","author":"Gueguinou","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"2019091012135163300_ref25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1517\/14728220903540257","article-title":"Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease","volume":"14","author":"Kohler","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"2019091012135163300_ref26","doi-asserted-by":"crossref","first-page":"R571","DOI":"10.1152\/ajpregu.00142.2014","article-title":"Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology","volume":"307","author":"Petkov","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2019091012135163300_ref27","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/ng.3282","article-title":"Mutations in KCNH1 and ATP6V1B2 cause Zimmermann\u2013Laband syndrome","volume":"47","author":"Kortum","year":"2015","journal-title":"Nat. Genet."},{"key":"2019091012135163300_ref28","doi-asserted-by":"crossref","first-page":"9474","DOI":"10.1073\/pnas.0401702101","article-title":"Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2+-activated K+ channel deficiency","volume":"101","author":"Sausbier","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2019091012135163300_ref29","doi-asserted-by":"crossref","first-page":"36746","DOI":"10.1074\/jbc.M405621200","article-title":"Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel","volume":"279","author":"Meredith","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2019091012135163300_ref30","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1038\/nn1740","article-title":"BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output","volume":"9","author":"Meredith","year":"2006","journal-title":"Nat. Neurosci."},{"key":"2019091012135163300_ref31","doi-asserted-by":"crossref","first-page":"12922","DOI":"10.1073\/pnas.0402660101","article-title":"Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BKbeta1-subunit leads to progressive hearing loss","volume":"101","author":"Ruttiger","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2019091012135163300_ref32","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.13137","article-title":"Survival and growth of C57BL\/6J mice lacking the BK channel, Kcnma1: lower adult body weight occurs together with higher body fat","volume":"5","author":"Halm","year":"2017","journal-title":"Physiol. Rep."},{"key":"2019091012135163300_ref33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neuropharm.2014.12.033","article-title":"Cognitive recovery by chronic activation of the large-conductance calcium-activated potassium channel in a mouse model of Alzheimer's disease","volume":"92","author":"Wang","year":"2015","journal-title":"Neuropharmacology"},{"key":"2019091012135163300_ref34","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13023-014-0124-6","article-title":"Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule","volume":"9","author":"Hebert","year":"2014","journal-title":"Orphanet. J. Rare Dis."},{"key":"2019091012135163300_ref35","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1523\/JNEUROSCI.3699-16.2017","article-title":"BK channels mediate synaptic plasticity underlying habituation in rats","volume":"37","author":"Zaman","year":"2017","journal-title":"J. Neurosci."},{"key":"2019091012135163300_ref36","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1161\/CIRCEP.111.000206","article-title":"MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome","volume":"6","author":"Chakrabarti","year":"2013","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"2019091012135163300_ref37","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/cge.12732","article-title":"Diagnostic odyssey in severe neurodevelopmental disorders: toward clinical whole-exome sequencing as a first-line diagnostic test","volume":"89","author":"Thevenon","year":"2016","journal-title":"Clin. Genet."},{"key":"2019091012135163300_ref38","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00438-015-1090-y","article-title":"Identification of rare variants in TNNI3 with atrial fibrillation in a Chinese GeneID population","volume":"291","author":"Wang","year":"2016","journal-title":"Mol. Genet. Genomics"},{"key":"2019091012135163300_ref39","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s00438-018-1417-6","article-title":"Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1","volume":"293","author":"Li","year":"2018","journal-title":"Mol. Genet. Genomics"},{"key":"2019091012135163300_ref40","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/32675","article-title":"Genetic basis and molecular mechanism for idiopathic ventricular fibrillation","volume":"392","author":"Chen","year":"1998","journal-title":"Nature"},{"key":"2019091012135163300_ref41","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.cell.2008.10.022","article-title":"Mutation in nuclear pore component NUP155 leads to atrial fibrillation and early sudden cardiac death","volume":"135","author":"Zhang","year":"2008","journal-title":"Cell"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddz117\/28935531\/ddz117.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/28\/17\/2937\/29207319\/ddz117.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,22]],"date-time":"2019-09-22T16:44:05Z","timestamp":1569170645000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/28\/17\/2937\/5506556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,15]]},"references-count":41,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2019,5,15]]},"published-print":{"date-parts":[[2019,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddz117","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,9,1]]},"published":{"date-parts":[[2019,5,15]]}}}