{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:20:54Z","timestamp":1779175254820,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Titin truncating variants (TTNtv) are the main genetic cause of dilated cardiomyopathies (DCMs). The phenotype and prognosis of probands have been evaluated in several large cohorts. However, few data are available on intrafamilial expressivity. To evaluate the phenotypical variability, we selected probands and family members carrying a unique\n                    <jats:italic>TTN<\/jats:italic>\n                    variant and recorded cardiac and genetic information. The cohort included 332 probands (314\n                    <jats:italic>TTNtv<\/jats:italic>\n                    probands and 18 probands with\n                    <jats:italic>in silico<\/jats:italic>\n                    predicted in\u2010frame exon skipping probands) and 191 relatives of\n                    <jats:italic>TTNtv<\/jats:italic>\n                    probands including 98 affected family members. Within\n                    <jats:italic>TTNtv<\/jats:italic>\n                    families, 96% of the affected relatives presented the same cardiomyopathy subtype as the proband, and 60% shared severity criteria (heart transplantation, implantable cardioverter\u2010defibrillator, personal sudden death). Furthermore, we reported 18 probands that carry predicted in\u2010frame exon skipping variants; they presented DCM (84%) as\n                    <jats:italic>TTN<\/jats:italic>\n                    tv patients but lower rate of rhythm disorders (0% vs. 29% respectively). In this work, we extend the genetic spectrum of\n                    <jats:italic>TTN<\/jats:italic>\n                    tv associated with DCM and show that within a family, and the cardiomyopathy phenotype is homogenous but the expressivity could vary. Such results are helpful for appropriate genetic counseling to better predict and manage the phenotype of mutation carriers.\n                  <\/jats:p>","DOI":"10.1111\/cge.14679","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T01:11:12Z","timestamp":1737594672000},"page":"425-433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Familial Phenotypic Variability Associated With\n                    <scp>TTN<\/scp>\n                    Truncating Variants in Cardiomyopathies: Variant Spectrum, Genotype\u2013Phenotype Correlation and\u00a0Consequences in Genetic Counseling"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3535-0847","authenticated-orcid":false,"given":"Marie","family":"Massier","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9\u2010 DMU BioGem\u2010Unit\u00e9 Fonctionnelle de Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique Mol\u00e9culaire et Cellulaire, Service de Biochimie M\u00e9tabolique APHP\u2010H\u00f4pital Universitaire Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"},{"name":"Service de g\u00e9n\u00e9tique Clinique, CHU Reims  Reims France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"de Groote","sequence":"additional","affiliation":[{"name":"CHU Lille, Service de Cardiologie  Lille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwan","family":"Donal","sequence":"additional","affiliation":[{"name":"Service de Cardiologie, CHU Rennes  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Magnin\u2010Poull","sequence":"additional","affiliation":[{"name":"Service de Cardiologie, CHU Nancy  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Coubes","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, CHU Montpellier  Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9350-8177","authenticated-orcid":false,"given":"Xavier","family":"Le Guillou Horn","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, CHU Poitiers  Poitiers France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Rooryck","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, CHU Bordeaux  Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"R\u00e9ant","sequence":"additional","affiliation":[{"name":"Service de Cardiologie, CHU Bordeaux  Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yann","family":"Troadec","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, CHU Caen  Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Claire","family":"Br\u00e9hin","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, CHU Rouen  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Proukhnitzky","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence Des Maladies Cardiaques h\u00e9r\u00e9ditaires H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Gandjbakhch","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence Des Maladies Cardiaques h\u00e9r\u00e9ditaires H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"},{"name":"INSERM UMRS1166 \u00c9quipe 1 ICAN Institute (Institut de cardiom\u00e9tabolisme et Nutrition)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Charron","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence Des Maladies Cardiaques h\u00e9r\u00e9ditaires H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"},{"name":"INSERM UMRS1166 \u00c9quipe 1 ICAN Institute (Institut de cardiom\u00e9tabolisme et Nutrition)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-3005","authenticated-orcid":false,"given":"Pascale","family":"Richard","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9\u2010 DMU BioGem\u2010Unit\u00e9 Fonctionnelle de Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique Mol\u00e9culaire et Cellulaire, Service de Biochimie M\u00e9tabolique APHP\u2010H\u00f4pital Universitaire Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"},{"name":"INSERM UMRS1166 \u00c9quipe 1 ICAN Institute (Institut de cardiom\u00e9tabolisme et Nutrition)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7891-3385","authenticated-orcid":false,"given":"Flavie","family":"Ader","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9\u2010 DMU BioGem\u2010Unit\u00e9 Fonctionnelle de Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique Mol\u00e9culaire et Cellulaire, Service de Biochimie M\u00e9tabolique APHP\u2010H\u00f4pital Universitaire Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"},{"name":"INSERM UMRS1166 \u00c9quipe 1 ICAN Institute (Institut de cardiom\u00e9tabolisme et Nutrition)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, UFR de Pharmacie  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng815"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh2301.100981"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110186"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.190"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006832"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq271"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13594"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13484"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.90"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv727"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad194"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.03.045"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ppedcard.2016.01.003"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12060883"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.11.037"},{"issue":"4","key":"e_1_2_11_18_1","first-page":"40","article-title":"Penetrance 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