156 Identification of novel variants associated with feline hypertrophic cardiomyopathy (HCM) using targeted next-generation sequencing

2021 ◽  
Vol 12 (1) ◽  
pp. 126
Author(s):  
Jade Raffle ◽  
Jose Novo Matos ◽  
Perry Elliott ◽  
David Connolly ◽  
Virginia Luis Fuentes ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hypertrophic Cardiomyopathy ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Novel Variants ◽  
Generation Sequencing

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

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1061
Author(s):  
Miruna Mihaela Micheu ◽  
Nicoleta-Monica Popa-Fotea ◽  
Nicoleta Oprescu ◽  
Stefan Bogdan ◽  
Monica Dan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hypertrophic Cardiomyopathy ◽  
Rare Variants ◽  
Causal Variant ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Novel Variants ◽  
Next Generation Sequencing Ngs ◽  
First Time ◽  
Generation Sequencing

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.

Genetic study of pediatric hypertrophic cardiomyopathy in Egypt

2020 ◽  
Vol 30 (12) ◽  
pp. 1910-1916
Author(s):  
Rania K. Darwish ◽  
Alireza Haghighi ◽  
Zeinab S. Seliem ◽  
Sonia A. El-Saiedi ◽  
Nora H. Radwan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hypertrophic Cardiomyopathy ◽  
Genetic Background ◽  
Rare Variants ◽  
National Study ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Egyptian Children ◽  
Generation Sequencing

AbstractPaediatric cardiomyopathy is a progressive and often lethal disorder and the most common cause of heart failure in children. Despite their severe outcomes, their genetic etiology is still poorly characterised. The current study aimed at uncovering the genetic background of idiopathic primary hypertrophic cardiomyopathy in a cohort of Egyptian children using targeted next-generation sequencing. The study included 24 patients (15 males and 9 females) presented to the cardiomyopathy clinic of Cairo University Children’s Hospital with a median age of 2.75 (0.5–14) years. Consanguinity was positive in 62.5% of patients. A family history of hypertrophic cardiomyopathy was present in 20.8% of patients. Ten rare variants were detected in eight patients; two pathogenic variants (8.3%) in MBPC3 and MYH7, and eight variants of uncertain significance in MYBPC3, TTN, VCL, MYL2, CSRP3, and RBM20.Here, we report on the first national study in Egypt that analysed sarcomeric and non-sarcomeric variants in a cohort of idiopathic paediatric hypertrophic cardiomyopathy patients using next-generation sequencing. The current pilot study suggests that paediatric hypertrophic cardiomyopathy in Egypt might have a particular genetic background, especially with the high burden of consanguinity. Including the genetic testing in the routine diagnostic service is important for a better understanding of the pathophysiology of the disease, proper patient management, and at-risk detection. Genome-wide tests (whole exome/genome sequencing) might be better than the targeted sequencing approach to test primary hypertrophic cardiomyopathy patients in addition to its ability for the identification of novel genetic causes.

scholarly journals Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy

2016 ◽  
Vol 38 (4) ◽  
pp. 1111-1124 ◽  
Author(s):  
Massimiliano Cecconi ◽  
Maria I. Parodi ◽  
Francesco Formisano ◽  
Paolo Spirito ◽  
Camillo Autore ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hypertrophic Cardiomyopathy ◽  
Phenotypic Heterogeneity ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Two novel variants in the ATM gene causing ataxia‐telangiectasia, including a duplication of 90 kb: Utility of targeted next‐generation sequencing in detection of copy number variation

2019 ◽  
Vol 83 (4) ◽  
pp. 266-273 ◽  
Author(s):  
Samuel Martin‐Rodriguez ◽  
Alicia Calvo‐Ferrer ◽  
Nerea Ortega‐Unanue ◽  
Laura Samaniego‐Jimenez ◽  
Maria Pilar Sanz‐Izquierdo ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Copy Number Variation ◽  
Ataxia Telangiectasia ◽  
Copy Number ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Novel Variants ◽  
Number Variation ◽  
Atm Gene ◽  
Generation Sequencing

scholarly journals In Silico Analysis of Novel Titin Non-Synonymous Missense Variants Detected by Targeted Next Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy

2021 ◽  
Vol 31 (3) ◽  
pp. 565-571
Author(s):  
Miruna Mihaela MICHEU ◽  
◽  
Nicoleta OPRESCU ◽  
Nicoleta-Monica POPA-FOTEA ◽  
◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hypertrophic Cardiomyopathy ◽  
In Silico ◽  
Sequence Variants ◽  
The Novel ◽  
Next Generation ◽  
Vast Number ◽  
Missense Variants ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Background and aim: Most of detected variants in cardiogenetic panels are still classified as variants of unknown significance, requiring supplementary analyses for a defi nite classifi cation. Performing further in-depth studies on such vast number of candidates is unfeasible. We sought to prioritise the novel nonsynonymous missense variants identified in titin gene (TTN) in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). Methods: 45 unrelated probands with HCM were screened by targeted next generation sequencing (NGS) covering all TTN exons. A stepwise strategy was used to select and prioritize the candidate variants for subsequent investigation. Results: Using rigorous bioinformatic filtering, 7 novel TTN nonsynonymous missense variants were identified and were the subject of in silico sequential analysis. 4 of the 7 variants were predicted to be possibly pathogenic by the Mendelian Clinically Applicable Pathogenicity (M-CAP) algorithm. Of these, three sequence variants (c.30392G>T, c.2518G>T, and c.49G>T) were also predicted to be destabilizing according to the second computational tool (TITINdb) and were designated as likely function-impacting. Conclusions: Herein we presented our strategy to hand-pick the novel TTN missense variants to be considered for further experimental studies. By applying various in silico tools, we restricted the list of sequence variants to be investigated to those most likely to be disease-associated, and thus reducing the need to perform expensive and time-consuming additional studies.

Sign in / Sign up

Export Citation Format

Share Document