{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T09:17:29Z","timestamp":1775207849279,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-899"],"award-info":[{"award-number":["075-15-2020-899"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Left ventricular noncompaction (LVNC) is a highly heterogeneous primary disorder of the myocardium. Its clinical features and genetic spectrum strongly overlap with other types of primary cardiomyopathies, in particular, hypertrophic cardiomyopathy. Study and the accumulation of genotype\u2013phenotype correlations are the way to improve the precision of our diagnostics. We present a familial case of LVNC with arrhythmic and thrombotic complications, myocardial fibrosis and heart failure, cosegregating with the splicing variant in the FHOD3 gene. This is the first description of FHOD3-dependent LVNC to our knowledge. We also revise the assumed mechanism of pathogenesis in the case of FHOD3 splicing alterations.<\/jats:p>","DOI":"10.3390\/genes13020309","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T08:38:48Z","timestamp":1644223128000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Case of Severe Left-Ventricular Noncompaction Associated with Splicing Altering Variant in the FHOD3 Gene"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9024-5364","authenticated-orcid":false,"given":"Roman","family":"Myasnikov","sequence":"first","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5932-1744","authenticated-orcid":false,"given":"Anna","family":"Bukaeva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"},{"name":"Federal State Budgetary Institution \u201cNational Medical Research Center of Endocrinology\u201d of the Ministry of Health of Russia, 115478 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3138-054X","authenticated-orcid":false,"given":"Olga","family":"Kulikova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5989-6233","authenticated-orcid":false,"given":"Alexey","family":"Meshkov","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4765-8021","authenticated-orcid":false,"given":"Anna","family":"Kiseleva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Ershova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Petukhova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"},{"name":"Federal State Budgetary Institution \u201cNational Medical Research Center of Endocrinology\u201d of the Ministry of Health of Russia, 115478 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6221-3659","authenticated-orcid":false,"given":"Mikhail","family":"Divashuk","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"},{"name":"All-Russia Research Institute of Agricultural Biotechnology, 127550 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5267-1832","authenticated-orcid":false,"given":"Evgenia","family":"Zotova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"},{"name":"Federal State Budgetary Institution \u201cNational Medical Research Center of Endocrinology\u201d of the Ministry of Health of Russia, 115478 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeniia","family":"Sotnikova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6855-4857","authenticated-orcid":false,"given":"Maria","family":"Kharlap","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Zharikova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"},{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Lomonosovsky Prospect 27, Building 10, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Vyatkin","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasily","family":"Ramensky","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-6447","authenticated-orcid":false,"given":"Alexandra","family":"Abisheva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"},{"name":"Federal State Budgetary Institution \u201cNational Medical Research Center of Endocrinology\u201d of the Ministry of Health of Russia, 115478 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisa","family":"Muraveva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"},{"name":"Federal State Budgetary Institution \u201cNational Medical Research Center of Endocrinology\u201d of the Ministry of Health of Russia, 115478 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6009-5775","authenticated-orcid":false,"given":"Sergey","family":"Koretskiy","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-8481","authenticated-orcid":false,"given":"Maria","family":"Kudryavtseva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Popov","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution \u201cNational Medical Research Center of Endocrinology\u201d of the Ministry of Health of Russia, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Utkina","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution \u201cNational Medical Research Center of Endocrinology\u201d of the Ministry of Health of Russia, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Mershina","sequence":"additional","affiliation":[{"name":"Medical Research and Educational Center, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5649-2193","authenticated-orcid":false,"given":"Valentin","family":"Sinitsyn","sequence":"additional","affiliation":[{"name":"Medical Research and Educational Center, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeniya","family":"Kogan","sequence":"additional","affiliation":[{"name":"Department of Faculty Therapy, I.M. Sechenov First Moscow Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-793X","authenticated-orcid":false,"given":"Olga","family":"Blagova","sequence":"additional","affiliation":[{"name":"Department of Faculty Therapy, I.M. Sechenov First Moscow Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oxana","family":"Drapkina","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/s41436-020-01049-x","article-title":"Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies","volume":"23","author":"Mazzarotto","year":"2021","journal-title":"Genet. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1186\/s13023-021-02112-9","article-title":"Overlap phenotypes of the left ventricular noncompaction and hypertrophic cardiomyopathy with complex arrhythmias and heart failure induced by the novel truncated DSC2 mutation","volume":"16","author":"Lin","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e009712","DOI":"10.1161\/CIRCIMAGING.119.009712","article-title":"Prognostic Significance of Left Ventricular Noncompaction","volume":"13","author":"Aung","year":"2020","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.jacc.2018.12.085","article-title":"Cardiac Phenotypes, Genetics, and Risks in Familial Noncompaction Cardiomyopathy","volume":"73","author":"Caliskan","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1093\/eurheartj\/ehx545","article-title":"Clinical genetics and outcome of left ventricular non-compaction cardiomyopathy","volume":"38","author":"Haas","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.jacc.2017.12.019","article-title":"Genetics, Clinical Features, and Long-Term Outcome of Noncompaction Cardiomyopathy","volume":"71","author":"Caliskan","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1074\/jbc.M117.813931","article-title":"The actin-organizing formin protein Fhod3 is required for postnatal development and functional maintenance of the adult heart in mice","volume":"293","author":"Ushijima","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1253\/circj.CJ-13-0255","article-title":"Dilated cardiomyopathy-associated FHOD3 variant impairs the ability to induce activation of transcription factor serum response factor","volume":"77","author":"Arimura","year":"2013","journal-title":"Circ. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1016\/j.jacc.2018.10.001","article-title":"Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy","volume":"72","author":"Ochoa","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s12265-013-9482-z","article-title":"The alternative heart: Impact of alternative splicing in heart disease","volume":"6","author":"Gatto","year":"2013","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_11","first-page":"1","article-title":"Genome-wide analysis of alternative splicing during human heart development","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Myasnikov, R., Brodehl, A., Meshkov, A., Kulikova, O., Kiseleva, A., Pohl, G.M., Sotnikova, E., Divashuk, M., Klimushina, M., and Zharikova, A. (2021). The Double Mutation DSG2-p.S363X and TBX20-p.D278X Is Associated with Left Ventricular Non-Compaction Cardiomyopathy: Case Report. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136775"},{"key":"ref_13","unstructured":"Li, H. (2013). Aligning Sequence Reads, Clone Sequences and Assembly Contigs with BWA-MEM. arXiv."},{"key":"ref_14","unstructured":"Van der Auwera, G.A., and O\u2019Connor, B.D. (2020). Genomics in the Cloud: Using Docker, GATK, and WDL in Terra, O\u2019Reilly Media, Inc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"ref_16","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."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1002\/humu.23626","article-title":"ClinGen Sequence Variant Interpretation Working Group (ClinGen SVI) Recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion","volume":"39","author":"Pesaran","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1136\/heart.86.6.666","article-title":"Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: A step towards classification as a distinct cardiomyopathy","volume":"86","author":"Jenni","year":"2001","journal-title":"Heart"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.ijcard.2011.08.845","article-title":"Refinement of echocardiographic criteria for left ventricular noncompaction","volume":"165","author":"Gerecke","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Barbitoff, Y.A., Khmelkova, D.N., Pomerantseva, E.A., Slepchenkov, A.V., Zubashenko, N.A., Mironova, I.V., Kaimonov, V.S., Polev, D.E., Tsay, V.V., and Glotov, A.S. (2021). Expanding the Russian allele frequency reference via cross-laboratory data integration: Insights from 6096 exome samples. bioRxiv.","DOI":"10.1101\/2021.11.02.21265801"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.jacc.2018.12.060","article-title":"Revisiting Genome Sequencing Data in Light of Novel Disease Gene Associations","volume":"73","author":"Semsarian","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_22","unstructured":"(2021, December 14). VCV000977175.1\u2014ClinVar\u2014NCBI. [cited 24 Nov 2021], Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/977175\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/cge.13759","article-title":"Deletions of specific exons of genes-1550496 detected by next-generation sequencing are associated with hypertrophic cardiomyopathy","volume":"98","author":"Ochoa","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e018236","DOI":"10.1161\/JAHA.120.018236","article-title":"Variant Spectrum of Formin Homology 2 Domain-Containing 3 Gene in Chinese Patients with Hypertrophic Cardiomyopathy","volume":"10","author":"Wu","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.tcm.2019.09.003","article-title":"Current understanding of fibrosis in genetic cardiomyopathies","volume":"30","author":"Eijgenraam","year":"2020","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/j.hlc.2021.04.008","article-title":"Fibrosis in Hypertrophic Cardiomyopathy Patients with and Without Sarcomere Gene Mutations","volume":"30","author":"Vullaganti","year":"2021","journal-title":"Heart Lung Circ."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12968-021-00718-3","article-title":"Effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in patients with hypertrophic cardiomyopathy","volume":"23","author":"Chung","year":"2021","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1093\/nar\/29.13.2850","article-title":"Genome-wide detection of alternative splicing in expressed sequences of human genes","volume":"29","author":"Modrek","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.omtn.2020.01.012","article-title":"Allele-Selective Knockdown of MYH7 Using Antisense Oligonucleotides","volume":"19","author":"Anderson","year":"2020","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1093\/eurheartj\/ehm429","article-title":"Cardiac beta-myosin heavy chain defects in two families with non-compaction cardiomyopathy: Linking non-compaction to hypertrophic, restrictive, and dilated cardiomyopathies","volume":"28","author":"Hoedemaekers","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1750-1172-7-45","article-title":"Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database","volume":"7","author":"Nicolas","year":"2012","journal-title":"Orphanet J. Rare Dis."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/309\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:15:28Z","timestamp":1760134528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,7]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["genes13020309"],"URL":"https:\/\/doi.org\/10.3390\/genes13020309","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,7]]}}}