Literature DB >> 33297573

Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy.

Miruna Mihaela Micheu1, Nicoleta-Monica Popa-Fotea1,2, Nicoleta Oprescu1, Stefan Bogdan1,2, Monica Dan1, Alexandru Deaconu1,2, Lucian Dorobantu1,3, Oana Gheorghe-Fronea1,2, Maria Greavu3, Corneliu Iorgulescu1, Alexandru Scafa-Udriste1,2, Razvan Ticulescu3, Radu Gabriel Vatasescu1,2, Maria Dorobanțu1,2.   

Abstract

BACKGROUND: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM).
METHODS: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM.
RESULTS: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel.
CONCLUSIONS: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification.

Entities:  

Keywords:  hypertrophic cardiomyopathy; next-generation sequencing; rare genetic variants

Year:  2020        PMID: 33297573      PMCID: PMC7762332          DOI: 10.3390/diagnostics10121061

Source DB:  PubMed          Journal:  Diagnostics (Basel)        ISSN: 2075-4418


  44 in total

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Authors:  Jeffrey B Geske; Steve R Ommen; Bernard J Gersh
Journal:  JACC Heart Fail       Date:  2018-04-11       Impact factor: 12.035

2.  Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy.

Authors:  Gilles Millat; Patrice Bouvagnet; Philippe Chevalier; Claire Dauphin; Pierre Simon Jouk; Antoine Da Costa; Fabienne Prieur; Jean-Luc Bresson; Laurence Faivre; Jean-Christophe Eicher; Nicolas Chassaing; Hervé Crehalet; Raphael Porcher; Claire Rodriguez-Lafrasse; Robert Rousson
Journal:  Eur J Med Genet       Date:  2010-07-30       Impact factor: 2.708

3.  Nationwide study on hypertrophic cardiomyopathy in Iceland: evidence of a MYBPC3 founder mutation.

Authors:  Berglind Adalsteinsdottir; Polakit Teekakirikul; Barry J Maron; Michael A Burke; Daniel F Gudbjartsson; Hilma Holm; Kari Stefansson; Steven R DePalma; Erica Mazaika; Barbara McDonough; Ragnar Danielsen; Jonathan G Seidman; Christine E Seidman; Gunnar T Gunnarsson
Journal:  Circulation       Date:  2014-07-30       Impact factor: 29.690

4.  Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations.

Authors:  Francesca Girolami; Carolyn Y Ho; Christopher Semsarian; Massimo Baldi; Melissa L Will; Katia Baldini; Francesca Torricelli; Laura Yeates; Franco Cecchi; Michael J Ackerman; Iacopo Olivotto
Journal:  J Am Coll Cardiol       Date:  2010-04-06       Impact factor: 24.094

5.  2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).

Authors:  Perry M Elliott; Aris Anastasakis; Michael A Borger; Martin Borggrefe; Franco Cecchi; Philippe Charron; Albert Alain Hagege; Antoine Lafont; Giuseppe Limongelli; Heiko Mahrholdt; William J McKenna; Jens Mogensen; Petros Nihoyannopoulos; Stefano Nistri; Petronella G Pieper; Burkert Pieske; Claudio Rapezzi; Frans H Rutten; Christoph Tillmanns; Hugh Watkins
Journal:  Eur Heart J       Date:  2014-08-29       Impact factor: 29.983

6.  Genetic Testing for Inherited Cardiovascular Diseases: A Scientific Statement From the American Heart Association.

Authors:  Kiran Musunuru; Ray E Hershberger; Sharlene M Day; N Jennifer Klinedinst; Andrew P Landstrom; Victoria N Parikh; Siddharth Prakash; Christopher Semsarian; Amy C Sturm
Journal:  Circ Genom Precis Med       Date:  2020-07-23

7.  Genetic basis and outcome in a nationwide study of Finnish patients with hypertrophic cardiomyopathy.

Authors:  Pertti Jääskeläinen; Jagadish Vangipurapu; Joose Raivo; Teemu Kuulasmaa; Tiina Heliö; Katriina Aalto-Setälä; Maija Kaartinen; Erkki Ilveskoski; Sari Vanninen; Liisa Hämäläinen; John Melin; Jorma Kokkonen; Markku S Nieminen; Markku Laakso; Johanna Kuusisto
Journal:  ESC Heart Fail       Date:  2019-02-18

Review 8.  Contemporary Insights Into the Genetics of Hypertrophic Cardiomyopathy: Toward a New Era in Clinical Testing?

Authors:  Francesco Mazzarotto; Iacopo Olivotto; Beatrice Boschi; Francesca Girolami; Corrado Poggesi; Paul J R Barton; Roddy Walsh
Journal:  J Am Heart Assoc       Date:  2020-04-18       Impact factor: 5.501

9.  Mitochondrial DNA: Hotspot for Potential Gene Modifiers Regulating Hypertrophic Cardiomyopathy.

Authors:  Parisa K Kargaran; Jared M Evans; Sara E Bodbin; James G W Smith; Timothy J Nelson; Chris Denning; Diogo Mosqueira
Journal:  J Clin Med       Date:  2020-07-23       Impact factor: 4.964

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Authors:  Róbert Sepp; Lidia Hategan; Beáta Csányi; János Borbás; Annamária Tringer; Eszter Dalma Pálinkás; Viktória Nagy; Hedvig Takács; Dóra Latinovics; Noémi Nyolczas; Attila Pálinkás; Réka Faludi; Miklós Rábai; Gábor Tamás Szabó; Dániel Czuriga; László Balogh; Róbert Halmosi; Attila Borbély; Tamás Habon; Zoltán Hegedűs; István Nagy
Journal:  Diagnostics (Basel)       Date:  2022-05-03

2.  Transaortic Shallow Septal Myectomy and Cutting of Secondary Fibrotic Mitral Valve Chordae-A 5-Year Single-Center Experience in the Treatment of Hypertrophic Obstructive Cardiomyopathy.

Authors:  Lucian Florin Dorobantu; Toma Andrei Iosifescu; Razvan Ticulescu; Maria Greavu; Maria Alexandrescu; Andrei Dermengiu; Miruna Mihaela Micheu; Monica Trofin
Journal:  J Clin Med       Date:  2022-05-30       Impact factor: 4.964

3.  The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy.

Authors:  Nicoleta-Monica Popa-Fotea; Miruna Mihaela Micheu; Nicoleta Oprescu; Adriana Alexandrescu; Maria Greavu; Sebastian Onciul; Roxana Onut; Ioana Petre; Alina Scarlatescu; Monica Stoian; Razvan Ticulescu; Diana Zamfir; Maria Dorobanțu
Journal:  Diagnostics (Basel)       Date:  2021-04-30

Review 4.  Inter-Species Rescue of Mutant Phenotype-The Standard for Genetic Analysis of Human Genetic Disorders in Drosophila melanogaster Model.

Authors:  Alexandru Al Ecovoiu; Attila Cristian Ratiu; Miruna Mihaela Micheu; Mariana Carmen Chifiriuc
Journal:  Int J Mol Sci       Date:  2022-02-27       Impact factor: 5.923

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