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The cardiac sodium channel mutation delQKP 1507-1509 is associated with the expanding phenotypic spectrum of LQT3, conduction disorder, dilated cardiomyopathy, and high incidence of youth sudden death.

Shi R, Zhang Y, Yang C, Huang C, Zhou X, Qiang H, Grace AA, Huang CL, Ma A - Europace (2008)

Bottom Line: Transthoracal echocardiography then revealed left ventricular dilatation and reduced systolic function.Two additional subjects died suddenly at 13 and 33 years.This data compliments and expands the spectrum of phenotypes resulting from this known gain-of-function mutation, including not only LQT3, cardiac conduction defects, and sudden death but also DCM, hitherto associated with loss-of-function mutations, for the first time.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Paediatrics, First Affiliated Hospital, Cardiovascular Ion Channel Disease Laboratory, Medical College of Xi'an Jiaotong University, Xi'an, Peoples Republic of China.

ABSTRACT

Aim: We report diverse phenotypic consequences of the delQKP-1507-1509 cardiac sodium channel mutation in three generations of a Chinese family.

Methods and results: Clinical and electrocardiographic (ECG), echocardiographic examination was followed by direct sequencing of SCN5A, KCNQ1, HERG, and LAMIN A/C to screen genomic DNA from blood samples. Of two mutation carriers, the proband was born with conduction disorders including second-degree atrioventricular (AV) block with prolonged QTc interval, additionally showing left anterior fascicular block (LAFB), incomplete right bundle-branch block (IRBBB), and intermittent third-degree AV block at 2 years, and clinical presentations of multiple syncope despite normal electroencephalograms at 8 years. Continuous ECG monitoring following presentation at 13 years revealed prolonged QTc and biphasic T-waves, multiple episodes of ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Transthoracal echocardiography then revealed left ventricular dilatation and reduced systolic function. Another mutation carrier showed features of long QT syndrome type 3 (LQT3), LAFB, and dilated cardiomyopathy (DCM). Two additional subjects died suddenly at 13 and 33 years.

Conclusion: This data compliments and expands the spectrum of phenotypes resulting from this known gain-of-function mutation, including not only LQT3, cardiac conduction defects, and sudden death but also DCM, hitherto associated with loss-of-function mutations, for the first time.

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Related in: MedlinePlus

Pedigree information of the family with the SCN5A-delQKP1507–1509 mutation. Filled squares denote affected male; filled circles denote affected female; open squares denote unaffected males; open circles denote unaffected females; pen square with a slash indicates deceased because of liver cancer; filled circles/square with a slash indicates sudden death and genotypes consequently are not available. Arrows indicate the proband.
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EUN202F1: Pedigree information of the family with the SCN5A-delQKP1507–1509 mutation. Filled squares denote affected male; filled circles denote affected female; open squares denote unaffected males; open circles denote unaffected females; pen square with a slash indicates deceased because of liver cancer; filled circles/square with a slash indicates sudden death and genotypes consequently are not available. Arrows indicate the proband.

Mentions: All investigations conformed to principles defined in the Helsinki Declaration. Eleven members of a three-generation Chinese family were investigated (Figure 1), informed written consent having been obtained from each member. They included a complete medical history, physical examination, at least two 12-lead ECG recordings obtained at different times and echocardiographic scanning. Heart rates, widths of P wave, PR intervals, QRS durations, and QT intervals corrected for heart rate using Bazett's formula (QTc) were measured in limb lead II. QTc intervals were averaged from five consecutive beats of at least two 12-lead ECG recordings at different time points. Resting echocardiography was performed by experts. Global function was digitized using an IE33 system (Philips Medical Systems, Eindhoven, The Netherlands) with 1–5 MHz broadband phased-array transducer connected. Biplane end-diastolic and end-systolic volumes were calculated from the planimetered areas by computer software according to a modified Simpson's rule. Two hundred unrelated control individuals were randomly selected from a group of Chinese healthy volunteers with normal 12-lead ECGs and without reported cardiovascular history.


The cardiac sodium channel mutation delQKP 1507-1509 is associated with the expanding phenotypic spectrum of LQT3, conduction disorder, dilated cardiomyopathy, and high incidence of youth sudden death.

Shi R, Zhang Y, Yang C, Huang C, Zhou X, Qiang H, Grace AA, Huang CL, Ma A - Europace (2008)

Pedigree information of the family with the SCN5A-delQKP1507–1509 mutation. Filled squares denote affected male; filled circles denote affected female; open squares denote unaffected males; open circles denote unaffected females; pen square with a slash indicates deceased because of liver cancer; filled circles/square with a slash indicates sudden death and genotypes consequently are not available. Arrows indicate the proband.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2573028&req=5

EUN202F1: Pedigree information of the family with the SCN5A-delQKP1507–1509 mutation. Filled squares denote affected male; filled circles denote affected female; open squares denote unaffected males; open circles denote unaffected females; pen square with a slash indicates deceased because of liver cancer; filled circles/square with a slash indicates sudden death and genotypes consequently are not available. Arrows indicate the proband.
Mentions: All investigations conformed to principles defined in the Helsinki Declaration. Eleven members of a three-generation Chinese family were investigated (Figure 1), informed written consent having been obtained from each member. They included a complete medical history, physical examination, at least two 12-lead ECG recordings obtained at different times and echocardiographic scanning. Heart rates, widths of P wave, PR intervals, QRS durations, and QT intervals corrected for heart rate using Bazett's formula (QTc) were measured in limb lead II. QTc intervals were averaged from five consecutive beats of at least two 12-lead ECG recordings at different time points. Resting echocardiography was performed by experts. Global function was digitized using an IE33 system (Philips Medical Systems, Eindhoven, The Netherlands) with 1–5 MHz broadband phased-array transducer connected. Biplane end-diastolic and end-systolic volumes were calculated from the planimetered areas by computer software according to a modified Simpson's rule. Two hundred unrelated control individuals were randomly selected from a group of Chinese healthy volunteers with normal 12-lead ECGs and without reported cardiovascular history.

Bottom Line: Transthoracal echocardiography then revealed left ventricular dilatation and reduced systolic function.Two additional subjects died suddenly at 13 and 33 years.This data compliments and expands the spectrum of phenotypes resulting from this known gain-of-function mutation, including not only LQT3, cardiac conduction defects, and sudden death but also DCM, hitherto associated with loss-of-function mutations, for the first time.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Paediatrics, First Affiliated Hospital, Cardiovascular Ion Channel Disease Laboratory, Medical College of Xi'an Jiaotong University, Xi'an, Peoples Republic of China.

ABSTRACT

Aim: We report diverse phenotypic consequences of the delQKP-1507-1509 cardiac sodium channel mutation in three generations of a Chinese family.

Methods and results: Clinical and electrocardiographic (ECG), echocardiographic examination was followed by direct sequencing of SCN5A, KCNQ1, HERG, and LAMIN A/C to screen genomic DNA from blood samples. Of two mutation carriers, the proband was born with conduction disorders including second-degree atrioventricular (AV) block with prolonged QTc interval, additionally showing left anterior fascicular block (LAFB), incomplete right bundle-branch block (IRBBB), and intermittent third-degree AV block at 2 years, and clinical presentations of multiple syncope despite normal electroencephalograms at 8 years. Continuous ECG monitoring following presentation at 13 years revealed prolonged QTc and biphasic T-waves, multiple episodes of ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Transthoracal echocardiography then revealed left ventricular dilatation and reduced systolic function. Another mutation carrier showed features of long QT syndrome type 3 (LQT3), LAFB, and dilated cardiomyopathy (DCM). Two additional subjects died suddenly at 13 and 33 years.

Conclusion: This data compliments and expands the spectrum of phenotypes resulting from this known gain-of-function mutation, including not only LQT3, cardiac conduction defects, and sudden death but also DCM, hitherto associated with loss-of-function mutations, for the first time.

Show MeSH
Related in: MedlinePlus