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The crucial role of titin in fetal development: recurrent miscarriages and bone, heart and muscle anomalies characterise the severe end of titinopathies spectrum.
Di Feo, Maria Francesca; Lillback, Victoria; Jokela, Manu; McEntagart, Meriel; Homfray, Tessa; Giorgio, Elisa; Casalis Cavalchini, Guido C; Brusco, Alfredo; Iascone, Maria; Spaccini, Luigina; D'Oria, Patrizia; Savarese, Marco; Udd, Bjarne.
Affiliation
  • Di Feo MF; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health (DINOGMI), University of Genoa, Genova, Italy mfrancesca.difeo@gmail.com.
  • Lillback V; Folkhälsan Research Center, Helsinki, Uusimaa, Finland.
  • Jokela M; University of Helsinki Department of Medical and Clinical Genetics, Helsinki, Uusimaa, Finland.
  • McEntagart M; Tampere University Hospital, Tampere, Pirkanmaa, Finland.
  • Homfray T; TYKS Turku University Hospital, Turku, Varsinais-Suomi, Finland.
  • Giorgio E; Department of Medical Genetics, St George's University of London, London, London, UK.
  • Casalis Cavalchini GC; St George's University of London, London, London, UK.
  • Brusco A; Department of Molecular Medicine, University of Pavia, Pavia, Lombardia, Italy.
  • Iascone M; Fondazione Istituto Neurologico Nazionale C Mondino Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Lombardia, Italy.
  • Spaccini L; Medical Genetics Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Piemonte, Italy.
  • D'Oria P; Department of Medical Sciences, University of Turin School of Medicine, Torino, Piemonte, Italy.
  • Savarese M; Laboratorio di Genetica Medica, ASST Papa Giovanni XXIII, Bergamo, BG, Italy.
  • Udd B; Unità di Genetica Medica, UOC Ostetricia e Ginecologia, Ospedale dei Bambini Vittore Buzzi, Milano, Lombardia, Italy.
J Med Genet ; 60(9): 866-873, 2023 09.
Article in En | MEDLINE | ID: mdl-36977548
BACKGROUND: Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/or cardiomyopathies. In homozygosity or in compound heterozygosity, they cause a wide spectrum of recessive phenotypes with a congenital or childhood onset. Most recessive phenotypes showing a congenital or childhood onset have been described in subjects carrying biallelic TTNtv in specific exons. Often karyotype or chromosomal microarray analyses are the only tests performed when prenatal anomalies are identified. Thereby, many cases caused by TTN defects might be missed in the diagnostic evaluations. In this study, we aimed to dissect the most severe end of the titinopathies spectrum. METHODS: We performed a retrospective study analysing an international cohort of 93 published and 10 unpublished cases carrying biallelic TTNtv. RESULTS: We identified recurrent clinical features showing a significant correlation with the genotype, including fetal akinesia (up to 62%), arthrogryposis (up to 85%), facial dysmorphisms (up to 73%), joint (up to 17%), bone (up to 22%) and heart anomalies (up to 27%) resembling complex, syndromic phenotypes. CONCLUSION: We suggest TTN to be carefully evaluated in any diagnostic process involving patients with these prenatal signs. This step will be essential to improve diagnostic performance, expand our knowledge and optimise prenatal genetic counselling.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Abortion, Habitual / Muscle, Skeletal / Connectin / Myocardium Type of study: Observational_studies / Risk_factors_studies Limits: Female / Humans / Pregnancy Language: En Journal: J Med Genet Year: 2023 Document type: Article Affiliation country: Italy Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Abortion, Habitual / Muscle, Skeletal / Connectin / Myocardium Type of study: Observational_studies / Risk_factors_studies Limits: Female / Humans / Pregnancy Language: En Journal: J Med Genet Year: 2023 Document type: Article Affiliation country: Italy Country of publication: United kingdom