schliessen

Filtern

 

Bibliotheken

210 Clinical Utility of Gene Panel and Clinical Exome Testing in Cardiac Disease

Cardiac disease is genetically heterogeneous with genes associated with multiple cardiac diseases, multiple causal genes per disease, and often multiple variants in one or more genes contributing to disease presentation. Gene panel testing, either through a specific targeted design, or by virtual an... Full description

Journal Title: Heart (British Cardiac Society) 2016-06, Vol.102 (Suppl 6), p.A139-A140
Main Author: Gable, Mary
Other Authors: Buxton, Chris , Woodward, Geoff , Wadsley, Marc , Honeychurch, Julie , Joanne, Davies , Newbury-Ecob, Ruth , Low, Karen , Donaldson, Alan , Affleck, Josphine , Whittington, Rebecca , Greenslade, Mark , Williams, Maggie
Format: Electronic Article Electronic Article
Language: English
Quelle: Alma/SFX Local Collection
Publisher: London: BMJ Publishing Group LTD
ID: ISSN: 1355-6037
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_proquest_journals_1793743436
title: 210 Clinical Utility of Gene Panel and Clinical Exome Testing in Cardiac Disease
format: Article
creator:
  • Gable, Mary
  • Buxton, Chris
  • Woodward, Geoff
  • Wadsley, Marc
  • Honeychurch, Julie
  • Joanne, Davies
  • Newbury-Ecob, Ruth
  • Low, Karen
  • Donaldson, Alan
  • Affleck, Josphine
  • Whittington, Rebecca
  • Greenslade, Mark
  • Williams, Maggie
ispartof: Heart (British Cardiac Society), 2016-06, Vol.102 (Suppl 6), p.A139-A140
description: Cardiac disease is genetically heterogeneous with genes associated with multiple cardiac diseases, multiple causal genes per disease, and often multiple variants in one or more genes contributing to disease presentation. Gene panel testing, either through a specific targeted design, or by virtual analysis from the exome/clinical exome is an ideal approach for genetic diagnosis and provides information regarding complexity of these diseases.Bristol Genetics Laboratory provides a targeted gene panel for paediatric cardiomyopathy (PC) (71 genes, Agilent SureSelect) and a variety of virtual gene panels from Agilent Focussed Exome; Congenital Heart Defect (CHD) (38 genes), Aortopathy (28 genes), Arrhythmia (54 genes), Cardiomyopathy (119 genes), Connective Tissue (42 genes) Molecular Autopsy (208 genes) and bicuspid aortic valve (8 genes). Whole clinical exome analysis (6110 genes) with phenotypic prioritisation of variants based on HPO terminology using Exomiser can also be performed for patients with complex phenotypes whose phenotype does not clearly fit into a pre-defined gene panel or for patients who tested negative for a specific panel. 133 patients have been tested, including newly diagnosed cardiac cases, patients negative for other cardiac gene testing, and patients who have phenotype/genotype incompatibility where contribution of more than one gene is suspected. 41/133 (30%) patients have at least one potentially pathogenic variant. 22 patients have multiple plausible variants.We present data from the cardiac cohort tested to date and cases illustrating the utility and complexity of gene panel testing for cardiac disease including; 1) A paediatric patient with Left Ventricular Non-Compaction (LVNC), dilated aortic root and sinus brachycardia heterozygous (on the PC 71 gene panel) for a novel TMEM43 variant c.994A>G, p.(Thr332Ala) of unknown clinical significance. Further testing using a bespoke 138 gene cardiac panel from the Focused Exome detected a novel splice variant in the HCN4 gene associated with LVNC and primary sinus brachycardia (Milano et al, 2014). This patient’s mother who has aortic dilation and regurgitation was heterozygous for the TMEM43 variant and the half-brother who also has dilated aortic root and LVNC did not carry either variant. 2) A large Dilated Cardiomyopathy (DCM) family with variable severity between family members, one affected cousin was heterozygous for a variant of uncertain significance in MYBPC3 c.3384G>C, p.(Glu11
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 1355-6037
fulltext: fulltext
issn:
  • 1355-6037
  • 1468-201X
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.425738
LOCALfalse
PrimoNMBib
record
control
sourceidproquest_cross
recordidTN_cdi_proquest_journals_1793743436
sourceformatXML
sourcesystemPC
sourcerecordid4077573531
originalsourceidFETCH-LOGICAL-11786-32c1962e2ca9902cc38fb9259e66f20c00d27380d793ffaa4e5649980c581e853
addsrcrecordideNqNkMFKAzEQhoMoWKvvEPC8dZLsZpOj1FqFgiIteAtpNqtZttmabMHevPiiPokpq549zTB8_8zwIYQJTAhh_OrV6tA3vs0oEJ4xkELChBI4QiOSc3EYPx-nnhVFxoGVp-gsxgYAcin4CD0l9Ovjc9o674xu8ap3rev3uKvx3HqLH7W3Lda-wn_I7L3bWLy0sXf-BTuPpzpUTht846LV0Z6jk1q30V781DFa3c6W07ts8TC_n14vMkJKkV6lhkhOLTVaSqDGMFGvJS2k5bymYAAqWjIBVSlZXWud24LnUgowhSBWFGyMLoe929C97dI7qul2waeTiqRMmbOc8USJgTKhizHYWm2D2-iwVwTUwaD6NagOBtVgUCUtKcqG6HrT_D_1DYJcdSs
sourcetypeAggregation Database
isCDItrue
recordtypearticle
pqid1793743436
display
typearticle
title210 Clinical Utility of Gene Panel and Clinical Exome Testing in Cardiac Disease
sourceAlma/SFX Local Collection
creatorGable, Mary ; Buxton, Chris ; Woodward, Geoff ; Wadsley, Marc ; Honeychurch, Julie ; Joanne, Davies ; Newbury-Ecob, Ruth ; Low, Karen ; Donaldson, Alan ; Affleck, Josphine ; Whittington, Rebecca ; Greenslade, Mark ; Williams, Maggie
creatorcontribGable, Mary ; Buxton, Chris ; Woodward, Geoff ; Wadsley, Marc ; Honeychurch, Julie ; Joanne, Davies ; Newbury-Ecob, Ruth ; Low, Karen ; Donaldson, Alan ; Affleck, Josphine ; Whittington, Rebecca ; Greenslade, Mark ; Williams, Maggie
descriptionCardiac disease is genetically heterogeneous with genes associated with multiple cardiac diseases, multiple causal genes per disease, and often multiple variants in one or more genes contributing to disease presentation. Gene panel testing, either through a specific targeted design, or by virtual analysis from the exome/clinical exome is an ideal approach for genetic diagnosis and provides information regarding complexity of these diseases.Bristol Genetics Laboratory provides a targeted gene panel for paediatric cardiomyopathy (PC) (71 genes, Agilent SureSelect) and a variety of virtual gene panels from Agilent Focussed Exome; Congenital Heart Defect (CHD) (38 genes), Aortopathy (28 genes), Arrhythmia (54 genes), Cardiomyopathy (119 genes), Connective Tissue (42 genes) Molecular Autopsy (208 genes) and bicuspid aortic valve (8 genes). Whole clinical exome analysis (6110 genes) with phenotypic prioritisation of variants based on HPO terminology using Exomiser can also be performed for patients with complex phenotypes whose phenotype does not clearly fit into a pre-defined gene panel or for patients who tested negative for a specific panel. 133 patients have been tested, including newly diagnosed cardiac cases, patients negative for other cardiac gene testing, and patients who have phenotype/genotype incompatibility where contribution of more than one gene is suspected. 41/133 (30%) patients have at least one potentially pathogenic variant. 22 patients have multiple plausible variants.We present data from the cardiac cohort tested to date and cases illustrating the utility and complexity of gene panel testing for cardiac disease including; 1) A paediatric patient with Left Ventricular Non-Compaction (LVNC), dilated aortic root and sinus brachycardia heterozygous (on the PC 71 gene panel) for a novel TMEM43 variant c.994A>G, p.(Thr332Ala) of unknown clinical significance. Further testing using a bespoke 138 gene cardiac panel from the Focused Exome detected a novel splice variant in the HCN4 gene associated with LVNC and primary sinus brachycardia (Milano et al, 2014). This patient’s mother who has aortic dilation and regurgitation was heterozygous for the TMEM43 variant and the half-brother who also has dilated aortic root and LVNC did not carry either variant. 2) A large Dilated Cardiomyopathy (DCM) family with variable severity between family members, one affected cousin was heterozygous for a variant of uncertain significance in MYBPC3 c.3384G>C, p.(Glu1128Asp) and another affected cousin heterozygous for a truncating TTN variant, c.89244del, p.(Phe29748Leufs*7). Further family studies are ongoing.Detailed phenotypic assessment (using a clinical proforma) has been shown to increase diagnostic yield in patients with complex cardiac disease.ReferenceMilano et al. J Am Coll Cardiol 2014;64(8):745–56
identifier
0ISSN: 1355-6037
1EISSN: 1468-201X
2DOI: 10.1136/heartjnl-2016-309890.210
languageeng
publisherLondon: BMJ Publishing Group LTD
ispartofHeart (British Cardiac Society), 2016-06, Vol.102 (Suppl 6), p.A139-A140
rights
02016, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
1Copyright: 2016 (c) 2016, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
thumbnail$$Usyndetics_thumb_exl
search
creatorcontrib
0Gable, Mary
1Buxton, Chris
2Woodward, Geoff
3Wadsley, Marc
4Honeychurch, Julie
5Joanne, Davies
6Newbury-Ecob, Ruth
7Low, Karen
8Donaldson, Alan
9Affleck, Josphine
10Whittington, Rebecca
11Greenslade, Mark
12Williams, Maggie
title
0210 Clinical Utility of Gene Panel and Clinical Exome Testing in Cardiac Disease
1Heart (British Cardiac Society)
descriptionCardiac disease is genetically heterogeneous with genes associated with multiple cardiac diseases, multiple causal genes per disease, and often multiple variants in one or more genes contributing to disease presentation. Gene panel testing, either through a specific targeted design, or by virtual analysis from the exome/clinical exome is an ideal approach for genetic diagnosis and provides information regarding complexity of these diseases.Bristol Genetics Laboratory provides a targeted gene panel for paediatric cardiomyopathy (PC) (71 genes, Agilent SureSelect) and a variety of virtual gene panels from Agilent Focussed Exome; Congenital Heart Defect (CHD) (38 genes), Aortopathy (28 genes), Arrhythmia (54 genes), Cardiomyopathy (119 genes), Connective Tissue (42 genes) Molecular Autopsy (208 genes) and bicuspid aortic valve (8 genes). Whole clinical exome analysis (6110 genes) with phenotypic prioritisation of variants based on HPO terminology using Exomiser can also be performed for patients with complex phenotypes whose phenotype does not clearly fit into a pre-defined gene panel or for patients who tested negative for a specific panel. 133 patients have been tested, including newly diagnosed cardiac cases, patients negative for other cardiac gene testing, and patients who have phenotype/genotype incompatibility where contribution of more than one gene is suspected. 41/133 (30%) patients have at least one potentially pathogenic variant. 22 patients have multiple plausible variants.We present data from the cardiac cohort tested to date and cases illustrating the utility and complexity of gene panel testing for cardiac disease including; 1) A paediatric patient with Left Ventricular Non-Compaction (LVNC), dilated aortic root and sinus brachycardia heterozygous (on the PC 71 gene panel) for a novel TMEM43 variant c.994A>G, p.(Thr332Ala) of unknown clinical significance. Further testing using a bespoke 138 gene cardiac panel from the Focused Exome detected a novel splice variant in the HCN4 gene associated with LVNC and primary sinus brachycardia (Milano et al, 2014). This patient’s mother who has aortic dilation and regurgitation was heterozygous for the TMEM43 variant and the half-brother who also has dilated aortic root and LVNC did not carry either variant. 2) A large Dilated Cardiomyopathy (DCM) family with variable severity between family members, one affected cousin was heterozygous for a variant of uncertain significance in MYBPC3 c.3384G>C, p.(Glu1128Asp) and another affected cousin heterozygous for a truncating TTN variant, c.89244del, p.(Phe29748Leufs*7). Further family studies are ongoing.Detailed phenotypic assessment (using a clinical proforma) has been shown to increase diagnostic yield in patients with complex cardiac disease.ReferenceMilano et al. J Am Coll Cardiol 2014;64(8):745–56
issn
01355-6037
11468-201X
fulltexttrue
rsrctypearticle
creationdate2016
recordtypearticle
recordideNqNkMFKAzEQhoMoWKvvEPC8dZLsZpOj1FqFgiIteAtpNqtZttmabMHevPiiPokpq549zTB8_8zwIYQJTAhh_OrV6tA3vs0oEJ4xkELChBI4QiOSc3EYPx-nnhVFxoGVp-gsxgYAcin4CD0l9Ovjc9o674xu8ap3rev3uKvx3HqLH7W3Lda-wn_I7L3bWLy0sXf-BTuPpzpUTht846LV0Z6jk1q30V781DFa3c6W07ts8TC_n14vMkJKkV6lhkhOLTVaSqDGMFGvJS2k5bymYAAqWjIBVSlZXWud24LnUgowhSBWFGyMLoe929C97dI7qul2waeTiqRMmbOc8USJgTKhizHYWm2D2-iwVwTUwaD6NagOBtVgUCUtKcqG6HrT_D_1DYJcdSs
startdate201606
enddate201606
creator
0Gable, Mary
1Buxton, Chris
2Woodward, Geoff
3Wadsley, Marc
4Honeychurch, Julie
5Joanne, Davies
6Newbury-Ecob, Ruth
7Low, Karen
8Donaldson, Alan
9Affleck, Josphine
10Whittington, Rebecca
11Greenslade, Mark
12Williams, Maggie
generalBMJ Publishing Group LTD
scope
0AAYXX
1CITATION
23V.
37X7
47XB
588E
688I
78AF
88FI
98FJ
108FK
11ABUWG
12AZQEC
13BENPR
14BTHHO
15DWQXO
16FYUFA
17GHDGH
18GNUQQ
19HCIFZ
20K9.
21M0S
22M1P
23M2P
24PQEST
25PQQKQ
26PQUKI
27PRINS
28Q9U
sort
creationdate201606
title210 Clinical Utility of Gene Panel and Clinical Exome Testing in Cardiac Disease
authorGable, Mary ; Buxton, Chris ; Woodward, Geoff ; Wadsley, Marc ; Honeychurch, Julie ; Joanne, Davies ; Newbury-Ecob, Ruth ; Low, Karen ; Donaldson, Alan ; Affleck, Josphine ; Whittington, Rebecca ; Greenslade, Mark ; Williams, Maggie
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-11786-32c1962e2ca9902cc38fb9259e66f20c00d27380d793ffaa4e5649980c581e853
rsrctypearticles
prefilterarticles
languageeng
creationdate2016
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Gable, Mary
1Buxton, Chris
2Woodward, Geoff
3Wadsley, Marc
4Honeychurch, Julie
5Joanne, Davies
6Newbury-Ecob, Ruth
7Low, Karen
8Donaldson, Alan
9Affleck, Josphine
10Whittington, Rebecca
11Greenslade, Mark
12Williams, Maggie
collection
0CrossRef
1ProQuest Central (Corporate)
2Health & Medical Collection
3ProQuest Central (purchase pre-March 2016)
4Medical Database (Alumni Edition)
5Science Database (Alumni Edition)
6STEM Database
7Hospital Premium Collection
8Hospital Premium Collection (Alumni Edition)
9ProQuest Central (Alumni) (purchase pre-March 2016)
10ProQuest Central (Alumni Edition)
11ProQuest Central Essentials
12ProQuest Central
13BMJ Journals
14ProQuest Central Korea
15Health Research Premium Collection
16Health Research Premium Collection (Alumni)
17ProQuest Central Student
18SciTech Premium Collection
19ProQuest Health & Medical Complete (Alumni)
20Health & Medical Collection (Alumni Edition)
21Medical Database
22Science Database
23ProQuest One Academic Eastern Edition
24ProQuest One Academic
25ProQuest One Academic UKI Edition
26ProQuest Central China
27ProQuest Central Basic
jtitleHeart (British Cardiac Society)
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Gable, Mary
1Buxton, Chris
2Woodward, Geoff
3Wadsley, Marc
4Honeychurch, Julie
5Joanne, Davies
6Newbury-Ecob, Ruth
7Low, Karen
8Donaldson, Alan
9Affleck, Josphine
10Whittington, Rebecca
11Greenslade, Mark
12Williams, Maggie
formatjournal
genrearticle
ristypeJOUR
atitle210 Clinical Utility of Gene Panel and Clinical Exome Testing in Cardiac Disease
jtitleHeart (British Cardiac Society)
date2016-06
risdate2016
volume102
issueSuppl 6
spageA139
epageA140
pagesA139-A140
issn1355-6037
eissn1468-201X
abstractCardiac disease is genetically heterogeneous with genes associated with multiple cardiac diseases, multiple causal genes per disease, and often multiple variants in one or more genes contributing to disease presentation. Gene panel testing, either through a specific targeted design, or by virtual analysis from the exome/clinical exome is an ideal approach for genetic diagnosis and provides information regarding complexity of these diseases.Bristol Genetics Laboratory provides a targeted gene panel for paediatric cardiomyopathy (PC) (71 genes, Agilent SureSelect) and a variety of virtual gene panels from Agilent Focussed Exome; Congenital Heart Defect (CHD) (38 genes), Aortopathy (28 genes), Arrhythmia (54 genes), Cardiomyopathy (119 genes), Connective Tissue (42 genes) Molecular Autopsy (208 genes) and bicuspid aortic valve (8 genes). Whole clinical exome analysis (6110 genes) with phenotypic prioritisation of variants based on HPO terminology using Exomiser can also be performed for patients with complex phenotypes whose phenotype does not clearly fit into a pre-defined gene panel or for patients who tested negative for a specific panel. 133 patients have been tested, including newly diagnosed cardiac cases, patients negative for other cardiac gene testing, and patients who have phenotype/genotype incompatibility where contribution of more than one gene is suspected. 41/133 (30%) patients have at least one potentially pathogenic variant. 22 patients have multiple plausible variants.We present data from the cardiac cohort tested to date and cases illustrating the utility and complexity of gene panel testing for cardiac disease including; 1) A paediatric patient with Left Ventricular Non-Compaction (LVNC), dilated aortic root and sinus brachycardia heterozygous (on the PC 71 gene panel) for a novel TMEM43 variant c.994A>G, p.(Thr332Ala) of unknown clinical significance. Further testing using a bespoke 138 gene cardiac panel from the Focused Exome detected a novel splice variant in the HCN4 gene associated with LVNC and primary sinus brachycardia (Milano et al, 2014). This patient’s mother who has aortic dilation and regurgitation was heterozygous for the TMEM43 variant and the half-brother who also has dilated aortic root and LVNC did not carry either variant. 2) A large Dilated Cardiomyopathy (DCM) family with variable severity between family members, one affected cousin was heterozygous for a variant of uncertain significance in MYBPC3 c.3384G>C, p.(Glu1128Asp) and another affected cousin heterozygous for a truncating TTN variant, c.89244del, p.(Phe29748Leufs*7). Further family studies are ongoing.Detailed phenotypic assessment (using a clinical proforma) has been shown to increase diagnostic yield in patients with complex cardiac disease.ReferenceMilano et al. J Am Coll Cardiol 2014;64(8):745–56
copLondon
pubBMJ Publishing Group LTD
doi10.1136/heartjnl-2016-309890.210