scholarly journals VP33.09: Exome sequencing versus gene panels for non‐immune hydrops fetalis

2020 ◽  
Vol 56 (S1) ◽  
pp. 196-196
Author(s):  
T. Sparks ◽  
J. Van Ziffle ◽  
P. Devine ◽  
B. Lianoglou ◽  
M.E. Norton
Keyword(s):  
Exome Sequencing ◽  
Hydrops Fetalis ◽  
Versus Gene ◽  
Gene Panels

Exome sequencing versus targeted gene panels for the evaluation of nonimmune hydrops fetalis

2021 ◽  
Author(s):  
Mary E. NORTON ◽  
Jessica VAN. ZIFFLE ◽  
Billie R. LIANOGLOU ◽  
Ugur HODOGLUGIL ◽  
W. Patrick DEVINE ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Hydrops Fetalis ◽  
Gene Panels ◽  
Nonimmune Hydrops

scholarly journals Next-Generation Sequencing Gene Panels and “Solo” Clinical Exome Sequencing Applied in Structurally Abnormal Fetuses

2021 ◽  
pp. 1-11
Author(s):  
Montse Pauta ◽  
Berta Campos ◽  
Maria Segura-Puimedon ◽  
Gemma Arca ◽  
Alfons Nadal ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Exome Sequencing ◽  
Diagnostic Yield ◽  
Monogenic Disease ◽  
Chromosomal Microarray Analysis ◽  
Next Generation ◽  
Clinical Exome Sequencing ◽  
Gene Panels ◽  
Generation Sequencing ◽  
Structural Anomalies

<b><i>Objective:</i></b> The aim of the study was to assess the diagnostic yield of 2 different next-generation sequencing (NGS) approaches: gene panel and “solo” clinical exome sequencing (solo-CES), in fetuses with structural anomalies and normal chromosomal microarray analysis (CMA), in the absence of a known familial mutation. <b><i>Methodology:</i></b> Gene panels encompassing from 2 to 140 genes, were applied mainly in persistent nuchal fold/fetal hydrops and in large hyperechogenic kidneys. Solo-CES, which entails sequencing the fetus alone and only interpreting the Online Mendelian Inheritance in Man genes, was performed in multisystem or recurrent structural anomalies. <b><i>Results:</i></b> During the study period (2015–2020), 153 NGS studies were performed in 148 structurally abnormal fetuses with a normal CMA. The overall diagnostic yield accounted for 35% (53/153) of samples and 36% (53/148) of the fetuses. Diagnostic yield with the gene panels was 31% (15/49), similar to 37% (38/104) in solo-CES. <b><i>Conclusions:</i></b> A monogenic disease was established as the underlying cause in 35% of selected fetal structural anomalies by gene panels and solo-CES.

scholarly journals Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Carina Heydt ◽  
Jan Rehker ◽  
Roberto Pappesch ◽  
Theresa Buhl ◽  
Markus Ball ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Large Gene ◽  
Mutational Burden ◽  
Whole Exome ◽  
Tumor Mutational Burden ◽  
Gene Panels

scholarly journals Value of Exome Sequencing in Diagnosis and Management of Recurrent Non-immune Hydrops Fetalis: A Retrospective Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyao Zhou ◽  
Jia Zhou ◽  
Xing Wei ◽  
Ruen Yao ◽  
Yingjun Yang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Pregnancy Outcome ◽  
Molecular Diagnosis ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Hydrops Fetalis ◽  
Intrauterine Fetal Death ◽  
Fetal Therapy ◽  
Inborn Errors ◽  
Prenatal Management

The purpose of the study was to use exome sequencing (ES) to study the contribution of single-gene disorders to recurrent non-immune hydrops fetalis (NIHF) and retrospectively evaluate the value of genetic diagnosis on prenatal management and pregnancy outcome. From January 2012 to October 2018, a cohort of 28 fetuses with recurrent NIHF was analyzed by trio ES. Fetuses with immune hydrops, non-genetic factors (including infection, etc.), karyotype, or CNV abnormalities were excluded. Variants were interpreted based on ACMG/AMP guidelines. Fetal therapy was performed on seven fetuses. Of the 28 fetuses, 10 (36%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in eight genes (GBA, GUSB, GBE1, RAPSN, FOXC2, PIEZO1, LZTR1, and FOXP3). Five (18%) fetuses had variant(s) of uncertain significance (VUS). Of the 10 fetuses with definitive molecular diagnosis, five (50%) were diagnosed with inborn errors of metabolism. Among the seven fetuses who received fetal therapy, two had definitive molecular diagnosis and resulted in neonatal death. Among the remaining five fetuses with negative results, four had newborn survival and one had intrauterine fetal death. Trio ES could facilitate genetic diagnosis of recurrent NIHF and improve the prenatal management and pregnancy outcome.

scholarly journals Dealing With Unspecific Clinical Phenotypes in Molecular Autopsy - HPO-Driven Whole Exome Sequencing Analysis Versus Gene Panel Testing

2020 ◽  
Author(s):  
Ulrike Schoen ◽  
Anna Holzer ◽  
Andreas Laner ◽  
Stephanie Kleinle ◽  
Florentine Scharf ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Gene Panel ◽  
Sequencing Analysis ◽  
Tissue Samples ◽  
Human Phenotype ◽  
Versus Gene ◽  
Molecular Autopsy ◽  
Whole Exome ◽  
Gene Panel Testing

Abstract Background: Molecular autopsy represents an efficient tool to save the diagnosis in up to one-third of sudden unexplained death (SUD). A defined gene panel is usually used for the examination. Alternatively, it is possible to carry out a comprehensive genetic assessment (Whole Exome Sequencing, WES), which also identifies rare, previously unknown variants. The disadvantage is that a dramatic number of variants must be assessed to identify the causal variant. To improve the evaluation of WES, the Human Phenotype Ontology (HPO) annotation is used internationally for deep phenotyping in the field of rare disease. However, a HPO-based evaluation of WES in SUD has not been described before.Methods: We performed WES in tissue samples from 16 people after SUD. Instead of a fixed gene panel, we defined a set of HPO terms and thus created a flexible “virtual gene panel”, with the advantage, that recently identified genes are automatically associated by HPO terms in the HPO database.Results: We obtained a median value of 68,947 variants per sample. Stringent filtering ended up in a median value of 276 variants per sample. Using the HPO-driven virtual gene panel we developed an algorithm that prioritized 1.4% of the variants. Variant interpretation resulted in eleven potentially causative variants in 16 individuals. Conclusion: Our data introduce an effective diagnostic procedure in molecular autopsy of SUD with a non-specific clinical phenotype.

scholarly journals Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis

2021 ◽  
Vol 41 (2) ◽  
pp. 91-92
Author(s):  
T.N. Sparks ◽  
B.R. Lianoglou ◽  
R.R. Adami ◽  
I.D. Pluym ◽  
K. Holliman ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Hydrops Fetalis ◽  
Nonimmune Hydrops

scholarly journals Whole Exome Sequencing Is the Minimal Technological Approach in Probands Born to Consanguineous Couples

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 962
Author(s):  
Francesca Peluso ◽  
Stefano Giuseppe Caraffi ◽  
Roberta Zuntini ◽  
Gabriele Trimarchi ◽  
Ivan Ivanovski ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Heart Defects ◽  
Complex Phenotype ◽  
Splicing Variant ◽  
Whole Exome ◽  
Brain Malformations ◽  
The Right ◽  
Gene Panels ◽  
Second Toe

We report on two siblings suffering from different pathogenic conditions, born to consanguineous parents. A multigene panel for brain malformations and microcephaly identified the homozygous splicing variant NM_005886.3:c.1416+1del in the KATNB1 gene in the older sister. On the other hand, exome sequencing revealed the homozygous frameshift variant NM_005245.4:c.9729del in the FAT1 gene in the younger sister, who had a more complex phenotype: in addition to bilateral anophthalmia and heart defects, she showed a right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. These features have been never reported before in patients with pathogenic FAT1 variants and support the role of this gene in the development of limb buds. Notably, each parent was heterozygous for both of these variants, which were ultra-rare and rare, respectively. This study raises awareness about the value of using whole exome/genome sequencing rather than targeted gene panels when testing affected offspring born to consanguineous couples. In this way, exomic data from the parents are also made available for carrier screening, to identify heterozygous pathogenetic and likely pathogenetic variants in genes responsible for other recessive conditions, which may pose a risk for subsequent pregnancies.

scholarly journals New Insights on Genetic Diagnostics in Cardiomyopathy and Arrhythmia Patients Gained by Stepwise Exome Data Analysis

2020 ◽  
Vol 9 (7) ◽  
pp. 2168
Author(s):  
Konstantinos Kolokotronis ◽  
Natalie Pluta ◽  
Eva Klopocki ◽  
Erdmute Kunstmann ◽  
Daniel Messroghli ◽  
...  
Keyword(s):  
Data Analysis ◽  
Exome Sequencing ◽  
Candidate Genes ◽  
Genetic Heterogeneity ◽  
Diagnostic Yield ◽  
Genetic Diagnostics ◽  
Routine Diagnostics ◽  
Exome Data ◽  
Gene Panels ◽  
Diagnostic Benefit

Inherited cardiomyopathies are characterized by clinical and genetic heterogeneity that challenge genetic diagnostics. In this study, we examined the diagnostic benefit of exome data compared to targeted gene panel analyses, and we propose new candidate genes. We performed exome sequencing in a cohort of 61 consecutive patients with a diagnosis of cardiomyopathy or primary arrhythmia, and we analyzed the data following a stepwise approach. Overall, in 64% of patients, a variant of interest (VOI) was detected. The detection rate in the main sub-cohort consisting of patients with dilated cardiomyopathy (DCM) was much higher than previously reported (25/36; 69%). The majority of VOIs were found in disease-specific panels, while a further analysis of an extended panel and exome data led to an additional diagnostic yield of 13% and 5%, respectively. Exome data analysis also detected variants in candidate genes whose functional profile suggested a probable pathogenetic role, the strongest candidate being a truncating variant in STK38. In conclusion, although the diagnostic yield of gene panels is acceptable for routine diagnostics, the genetic heterogeneity of cardiomyopathies and the presence of still-unknown causes favor exome sequencing, which enables the detection of interesting phenotype–genotype correlations, as well as the identification of novel candidate genes.

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