scholarly journals Clinicopathological and Genetic Profiles of Cases with Myocytes Disarray—Investigation for Establishing the Autopsy Diagnostic Criteria for Hypertrophic Cardiomyopathy

2019 ◽  
Vol 8 (4) ◽  
pp. 463 ◽  
Author(s):  
Yukiko Hata ◽  
Shojiro Ichimata ◽  
Yoshiaki Yamaguchi ◽  
Keiichi Hirono ◽  
Yuko Oku ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hypertrophic Cardiomyopathy ◽  
Cardiac Death ◽  
Rare Variants ◽  
The Other ◽  
Diagnostic Pitfall ◽  
Genetic Profiles ◽  
Diagnostic Criterion ◽  
Generation Sequencing ◽  
Myocyte Disarray

Myocyte disarray of >10% in the heart is broadly accepted as a diagnostic pitfall for hypertrophic cardiomyopathy (HCM) at postmortem. The present study aims to propose an additional diagnostic criterion of HCM. Heart specimens from 1387 serial forensic autopsy cases were examined. Cases with myocyte disarray were extracted and applied to morphometric analysis to determine the amount of myocyte disarray. Comprehensive genetic analysis by using next-generation sequencing was subsequently applied for cases with myocyte disarray. Fifteen cases with myocyte disarray were extracted as candidate cases (1.1%, 11 men and 4 women, aged 48–94 years). In terms of the cause of death, only 2 cases were cardiac or possible cardiac death, and the other was non-cardiac death. Six cases showed myocyte disarray of >10% and 3 cases showed myocyte disarray of 5% to 10%. The other 6 cases showed myocyte disarray of <5%. Nine rare variants in 5 HCM-related genes (MYBPC3, MYH7, MYH6, PRKAG2, and CAV3) were found in 8 of 9 cases with myocyte disarray of >5%. The remaining 1 and 6 cases with myocyte disarray of <5% did not have any such variant. Myocyte disarray of >5% with rare variants in related genes might be an appropriate postmortem diagnostic criterion for HCM, in addition to myocyte disarray of 10%.

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 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.

scholarly journals Clinical and Genetic Spectrum of Stargardt Disease in Argentinean Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Marcela D. Mena ◽  
Angélica A. Moresco ◽  
Sofía H. Vidal ◽  
Diana Aguilar-Cortes ◽  
María G. Obregon ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Next Generation Sequencing ◽  
Final Analysis ◽  
The Other ◽  
South American ◽  
Stargardt Disease ◽  
Targeted Next Generation Sequencing ◽  
Mutational Spectrum ◽  
Genetic Features ◽  
Generation Sequencing

PurposeTo describe the clinical and molecular spectrum of Stargardt disease (STGD) in a cohort of Argentinean patients.MethodsThis retrospective study included 132 subjects comprising 95 probands clinically diagnosed with STGD and relatives from 16 of them. Targeted next-generation sequencing of the coding and splicing regions of ABCA4 and other phenocopying genes (ELOVL4, PROM1, and CNGB3) was performed in 97 STGD patients.ResultsWe found two or more disease-causing variants in the ABCA4 gene in 69/95 (73%) probands, a single ABCA4 variant in 9/95 (9.5%) probands, and no ABCA4 variants in 17/95 (18%) probands. The final analysis identified 173 variants in ABCA4. Seventy-nine ABCA4 variants were unique, of which nine were novel. No significant findings were seen in the other evaluated genes.ConclusionThis study describes the phenotypic and genetic features of STGD1 in an Argentinean cohort. The mutations p.(Gly1961Glu) and p.(Arg1129Leu) were the most frequent, representing almost 20% of the mutated alleles. We also expanded the ABCA4 mutational spectrum with nine novel disease-causing variants, of which eight might be associated with South American natives.

HADHA and HADHB gene associated phenotypes - Identification of rare variants in a patient cohort by Next Generation Sequencing

2019 ◽  
Vol 44 ◽  
pp. 14-20 ◽  
Author(s):  
Isabel Diebold ◽  
Ulrike Schön ◽  
Rita Horvath ◽  
Oliver Schwartz ◽  
Elke Holinski-Feder ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Rare Variants ◽  
Next Generation ◽  
Patient Cohort ◽  
Generation Sequencing
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