Josine M de Winter, Karlijn Bouman, Joshua Strom, Mei Methawasin, Jan D H Jongbloed, Wilma van der Roest, Jan van Wijngaarden, Janneke Timmermans, Robin Nijveldt, Frederik van den Heuvel, Erik-Jan Kamsteeg, Baziel G van Engelen, Ricardo Galli, Sylvia J P Bogaards, Reinier A Boon, Robbert J van der Pijl, Henk Granzier, Bobby Koeleman, Ahmad S Amin, Jolanda van der Velden, J Peter van Tintelen, Maarten P van den Berg, Karin Y van Spaendonck-Zwarts, Nicol C Voermans, Coen A C Ottenheijm
{"title":"KBTBD13是一种新的心肌病基因。","authors":"Josine M de Winter, Karlijn Bouman, Joshua Strom, Mei Methawasin, Jan D H Jongbloed, Wilma van der Roest, Jan van Wijngaarden, Janneke Timmermans, Robin Nijveldt, Frederik van den Heuvel, Erik-Jan Kamsteeg, Baziel G van Engelen, Ricardo Galli, Sylvia J P Bogaards, Reinier A Boon, Robbert J van der Pijl, Henk Granzier, Bobby Koeleman, Ahmad S Amin, Jolanda van der Velden, J Peter van Tintelen, Maarten P van den Berg, Karin Y van Spaendonck-Zwarts, Nicol C Voermans, Coen A C Ottenheijm","doi":"10.1002/humu.24499","DOIUrl":null,"url":null,"abstract":"<p><p>KBTBD13 variants cause nemaline myopathy type 6 (NEM6). The majority of NEM6 patients harbors the Dutch founder variant, c.1222C>T, p.Arg408Cys (KBTBD13 p.R408C). Although KBTBD13 is expressed in cardiac muscle, cardiac involvement in NEM6 is unknown. Here, we constructed pedigrees of three families with the KBTBD13 p.R408C variant. In 65 evaluated patients, 12% presented with left ventricle dilatation, 29% with left ventricular ejection fraction< 50%, 8% with atrial fibrillation, 9% with ventricular tachycardia, and 20% with repolarization abnormalities. Five patients received an implantable cardioverter defibrillator, three cases of sudden cardiac death were reported. Linkage analysis confirmed cosegregation of the KBTBD13 p.R408C variant with the cardiac phenotype. Mouse studies revealed that (1) mice harboring the Kbtbd13 p.R408C variant display mild diastolic dysfunction; (2) Kbtbd13-deficient mice have systolic dysfunction. Hence, (1) KBTBD13 is associated with cardiac dysfunction and cardiomyopathy; (2) KBTBD13 should be added to the cardiomyopathy gene panel; (3) NEM6 patients should be referred to the cardiologist.</p>","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"43 12","pages":"1860-1865"},"PeriodicalIF":3.3000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/ba/HUMU-43-1860.PMC10100581.pdf","citationCount":"0","resultStr":"{\"title\":\"KBTBD13 is a novel cardiomyopathy gene.\",\"authors\":\"Josine M de Winter, Karlijn Bouman, Joshua Strom, Mei Methawasin, Jan D H Jongbloed, Wilma van der Roest, Jan van Wijngaarden, Janneke Timmermans, Robin Nijveldt, Frederik van den Heuvel, Erik-Jan Kamsteeg, Baziel G van Engelen, Ricardo Galli, Sylvia J P Bogaards, Reinier A Boon, Robbert J van der Pijl, Henk Granzier, Bobby Koeleman, Ahmad S Amin, Jolanda van der Velden, J Peter van Tintelen, Maarten P van den Berg, Karin Y van Spaendonck-Zwarts, Nicol C Voermans, Coen A C Ottenheijm\",\"doi\":\"10.1002/humu.24499\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>KBTBD13 variants cause nemaline myopathy type 6 (NEM6). The majority of NEM6 patients harbors the Dutch founder variant, c.1222C>T, p.Arg408Cys (KBTBD13 p.R408C). Although KBTBD13 is expressed in cardiac muscle, cardiac involvement in NEM6 is unknown. Here, we constructed pedigrees of three families with the KBTBD13 p.R408C variant. In 65 evaluated patients, 12% presented with left ventricle dilatation, 29% with left ventricular ejection fraction< 50%, 8% with atrial fibrillation, 9% with ventricular tachycardia, and 20% with repolarization abnormalities. Five patients received an implantable cardioverter defibrillator, three cases of sudden cardiac death were reported. Linkage analysis confirmed cosegregation of the KBTBD13 p.R408C variant with the cardiac phenotype. Mouse studies revealed that (1) mice harboring the Kbtbd13 p.R408C variant display mild diastolic dysfunction; (2) Kbtbd13-deficient mice have systolic dysfunction. Hence, (1) KBTBD13 is associated with cardiac dysfunction and cardiomyopathy; (2) KBTBD13 should be added to the cardiomyopathy gene panel; (3) NEM6 patients should be referred to the cardiologist.</p>\",\"PeriodicalId\":13061,\"journal\":{\"name\":\"Human Mutation\",\"volume\":\"43 12\",\"pages\":\"1860-1865\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/ba/HUMU-43-1860.PMC10100581.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human Mutation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/humu.24499\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Mutation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/humu.24499","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
KBTBD13 variants cause nemaline myopathy type 6 (NEM6). The majority of NEM6 patients harbors the Dutch founder variant, c.1222C>T, p.Arg408Cys (KBTBD13 p.R408C). Although KBTBD13 is expressed in cardiac muscle, cardiac involvement in NEM6 is unknown. Here, we constructed pedigrees of three families with the KBTBD13 p.R408C variant. In 65 evaluated patients, 12% presented with left ventricle dilatation, 29% with left ventricular ejection fraction< 50%, 8% with atrial fibrillation, 9% with ventricular tachycardia, and 20% with repolarization abnormalities. Five patients received an implantable cardioverter defibrillator, three cases of sudden cardiac death were reported. Linkage analysis confirmed cosegregation of the KBTBD13 p.R408C variant with the cardiac phenotype. Mouse studies revealed that (1) mice harboring the Kbtbd13 p.R408C variant display mild diastolic dysfunction; (2) Kbtbd13-deficient mice have systolic dysfunction. Hence, (1) KBTBD13 is associated with cardiac dysfunction and cardiomyopathy; (2) KBTBD13 should be added to the cardiomyopathy gene panel; (3) NEM6 patients should be referred to the cardiologist.
期刊介绍：
Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.
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