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Array comparative genomic hybridization identifies a heterozygous deletion of exon 3 of the RYR2 gene.

Leong IU, Sucich J, Prosser DO, Skinner JR, Crawford JR, Higgins C, Love DR - Ups. J. Med. Sci. (2015)

Bottom Line: The standard diagnostic screening involves Sanger-based sequencing of 45 of the 105 translated exons of the RYR2 gene, and copy number changes of a limited number of exons that are detected using multiplex ligation-dependent probe amplification (MLPA).The CGH array detected a 1.1 kb deletion encompassing exon 3 of the RYR2 gene.The aCGH method offers significant advantages over MLPA in genetic screening for heritable cardiac disorders.

View Article: PubMed Central - PubMed

Affiliation: Diagnostic Genetics, LabPLUS, Auckland City Hospital , PO Box 110031, Auckland 1142 , New Zealand.

ABSTRACT

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a heritable cardiac disorder characterized by life-threatening ventricular tachycardia caused by exercise or acute emotional stress. The standard diagnostic screening involves Sanger-based sequencing of 45 of the 105 translated exons of the RYR2 gene, and copy number changes of a limited number of exons that are detected using multiplex ligation-dependent probe amplification (MLPA).

Methods: In the current study, a previously validated bespoke array comparative genomic hybridization (aCGH) technique was used to detect copy number changes in the RYR2 gene in a 43-year-old woman clinically diagnosed with CPVT.

Results: The CGH array detected a 1.1 kb deletion encompassing exon 3 of the RYR2 gene. This is the first report using the aCGH technique to screen for mutations causing CPVT.

Conclusions: The aCGH method offers significant advantages over MLPA in genetic screening for heritable cardiac disorders.

No MeSH data available.


Related in: MedlinePlus

Pedigree of the RYR2 exon 3 deletion carriers. The proband (II-3) is indicated by the black arrow. Family members carrying the RYR2 exon 3 deletion are indicated in solid black. The members with unknown clinical and genetic background information are indicated by ?.
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Figure 1: Pedigree of the RYR2 exon 3 deletion carriers. The proband (II-3) is indicated by the black arrow. Family members carrying the RYR2 exon 3 deletion are indicated in solid black. The members with unknown clinical and genetic background information are indicated by ?.

Mentions: The proband (II-3) was a 43-year-old woman who was suspected to have CPVT, and she was referred to the Cardiac Inherited Disease Group (CIDG) of Auckland City Hospital for further cardiac/genetic investigation (Figure 1). The proband had previously experienced syncope with exertion and multiple ventricular premature complexes (VPCs) whilst monitored (Figure 2A). An exercise tolerance test (ETT) showed runs of polymorphic ventricular tachycardia (VT) with minimal exertion, and echocardiography confirmed a structurally normal heart. She was managed with beta-blockade and an implantable cardioverter-defibrillator (ICD). To control further the VT episodes she later underwent a left thoracoscopic sympathectomy and more recently has responded well to flecainide.


Array comparative genomic hybridization identifies a heterozygous deletion of exon 3 of the RYR2 gene.

Leong IU, Sucich J, Prosser DO, Skinner JR, Crawford JR, Higgins C, Love DR - Ups. J. Med. Sci. (2015)

Pedigree of the RYR2 exon 3 deletion carriers. The proband (II-3) is indicated by the black arrow. Family members carrying the RYR2 exon 3 deletion are indicated in solid black. The members with unknown clinical and genetic background information are indicated by ?.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526874&req=5

Figure 1: Pedigree of the RYR2 exon 3 deletion carriers. The proband (II-3) is indicated by the black arrow. Family members carrying the RYR2 exon 3 deletion are indicated in solid black. The members with unknown clinical and genetic background information are indicated by ?.
Mentions: The proband (II-3) was a 43-year-old woman who was suspected to have CPVT, and she was referred to the Cardiac Inherited Disease Group (CIDG) of Auckland City Hospital for further cardiac/genetic investigation (Figure 1). The proband had previously experienced syncope with exertion and multiple ventricular premature complexes (VPCs) whilst monitored (Figure 2A). An exercise tolerance test (ETT) showed runs of polymorphic ventricular tachycardia (VT) with minimal exertion, and echocardiography confirmed a structurally normal heart. She was managed with beta-blockade and an implantable cardioverter-defibrillator (ICD). To control further the VT episodes she later underwent a left thoracoscopic sympathectomy and more recently has responded well to flecainide.

Bottom Line: The standard diagnostic screening involves Sanger-based sequencing of 45 of the 105 translated exons of the RYR2 gene, and copy number changes of a limited number of exons that are detected using multiplex ligation-dependent probe amplification (MLPA).The CGH array detected a 1.1 kb deletion encompassing exon 3 of the RYR2 gene.The aCGH method offers significant advantages over MLPA in genetic screening for heritable cardiac disorders.

View Article: PubMed Central - PubMed

Affiliation: Diagnostic Genetics, LabPLUS, Auckland City Hospital , PO Box 110031, Auckland 1142 , New Zealand.

ABSTRACT

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a heritable cardiac disorder characterized by life-threatening ventricular tachycardia caused by exercise or acute emotional stress. The standard diagnostic screening involves Sanger-based sequencing of 45 of the 105 translated exons of the RYR2 gene, and copy number changes of a limited number of exons that are detected using multiplex ligation-dependent probe amplification (MLPA).

Methods: In the current study, a previously validated bespoke array comparative genomic hybridization (aCGH) technique was used to detect copy number changes in the RYR2 gene in a 43-year-old woman clinically diagnosed with CPVT.

Results: The CGH array detected a 1.1 kb deletion encompassing exon 3 of the RYR2 gene. This is the first report using the aCGH technique to screen for mutations causing CPVT.

Conclusions: The aCGH method offers significant advantages over MLPA in genetic screening for heritable cardiac disorders.

No MeSH data available.


Related in: MedlinePlus