Postmortem genetic screening of SNPs in RyR2 gene in sudden unexplained nocturnal death syndrome in the southern Chinese Han population

Huang, Lei; Liu, Chao; Tang, Shifu; Su, Terry; Cheng, Jianding

doi:10.1016/j.forsciint.2013.12.007

Cited by 18 publications

(25 citation statements)

References 28 publications

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“…All SUNDS and BrS cases with SCN10A rare variants were negative for pathogenic rare variants in arrhythmiasassociated genes (SCN5A, SCN1B-4B, MOG1, GPD1-L, RyR2, PKP2, KCNQ1, KCNH2, KCNE1, KCNE2, and DSP) as we previously detected and reported [15,[23][24][25][26]. …”

Section: Rare Variants In Chinese Sporadic Sunds and Brs Casessupporting

confidence: 64%

“…Due to the low frequency in public database and the absence of pathogenic rare variants in arrhythmia-related genes [15,[23][24][25][26], all these identified SCN10A rare variants in both SUNDS and BrS (especially the Bpathogenic^or Blikely pathogenic^variants) may account for the corresponding SUNDS or BrS cases. These pathogenic or BbenignŜ CN10A rare variants are being characterized by us using cellular electrophysiological functional methods to elucidate the biophysical mechanisms underlying SUNDS.…”

Section: Discussionmentioning

confidence: 99%

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Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population

et al. 2016

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Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unknown etiology to both forensic pathologists and physicians. The electrocardiogram (ECG) characteristics and clinical phenotype of SUNDS survivors strongly suggest that SUNDS shares some similarities with Brugada syndrome (BrS). Recently, the variants of sodium channel Na 1.8 coding gene SCN10A were identified to be associated with BrS. Here, we investigated the association of SCN10A gene variants with 105 sporadic SUNDS victims and 22 BrS cases in the Chinese Han population. A total of 6 rare mutations and 16 polymorphisms were detected in SUNDS victims. Of the six rare mutations, two were putative pathogenic mutations (F386C and R1263*), one was a likely pathogenic mutation (R14H), and the other three were predicted as benign (R817Q, T1181M, and P1683S). As for the 16 polymorphisms, 1 was a novel polymorphism (c.4144-84G>A) located in intron 24, and the rest were reported previously including one polymorphism (c.2884A>G [I962V]) which showed a statistically significant difference in allele frequency (p = 0.044) between SUNDS and the control group. There were also 5 rare mutations and 15 polymorphisms detected in BrS cases. This is the first report of common and rare variants of SCN10A gene in SUNDS and BrS in the Chinese Han population, which provides the genetic epidemiological evidence that SCN10A may be a novel susceptibility gene for SUNDS and account for approximately 3 % of SUNDS in China.

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Section: Rare Variants In Chinese Sporadic Sunds and Brs Casessupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population

et al. 2016

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“…Sudden unexplained nocturnal death syndrome (SUNDS) is a perplexing disorder often presenting to forensic pathologists [1–3]. SUNDS prevails in Southeast Asia and has some common clinical features: (1) the majority of the decedents are male, apparently healthy, 20 to 50 years old; (2) the death mostly occurred at night during sleep or at rest; (3) no evident histopathology changes explain the cause of death.…”

Section: Introductionmentioning

confidence: 99%

“…We have performed postmortem molecular autopsy in sporadic cases of SUNDS on the lethal cardiac arrhythmia-associated genes (SCN5A, SCN1B-4B, GPD1L, MOG1, KCNQ1, KCNH2, KCNE1, KCNE2, and RyR2) in the southern Chinese Han population and found that inherited cardiacarrhythmias, such as LQTS, BrS, CPVT and ARVC may explain the cause of death in just under 20% of SUNDS [1–3], leaving unclear the genetic etiology of more than 80% of SUNDS. With the goal of identifying additional genes associated with SUNDS, in this study we screened our SUNDS cohort for variants in the DSP gene.…”

Section: Introductionmentioning

confidence: 99%

Identification of rare variants of DSP gene in sudden unexplained nocturnal death syndrome in the southern Chinese Han population

et al. 2015

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Sudden unexplained nocturnal death syndrome (SUNDS) is a perplexing disorder to both forensic pathologists and clinic physicians. Desmoplakin (DSP) gene was the first desmosomal gene linked to arrhythmogenic right ventricular cardiomyopathy (ARVC) which was associated with sudden death. To identify the genetic variants of the DSP gene in SUNDS in the southern Chinese Han population, we genetically screened the DSP gene in 40 sporadic SUNDS victims, 16 Brugada syndrome (BrS) patients and 2 Early Repolarization syndrome (ERS) patients using Next Generation Sequencing (NSG) and direct Sanger sequencing. A total of 10 genetic variants of the DSP gene were detected in 11 cases, comprised of two novel missense mutations (p.I125F and p.D521A) and eight previously reported rare variants. Of eight reported variants, two were previously considered pathogenic (p.Q90R and p.R2639Q), three were predicted in silico to bepathogenic (p.R315C, p.E1357D and p.D2579H), and the rest three were predicted to be benign (p.N1234S, p.R1308Q and p.T2267S). This is the first report of DSP genetic screening in Chinese SUNDS and Brugada syndrome. Our results implies that DSP mutations contribute to the genetic cause of some SUNDS victims and maybe a new susceptible gene for Brugada syndrome.

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“…4,9 While structural diseases such as cardiac conduction system (CCS) abnormalities and acute hemorrhagic pancreatitis account rarely for the death of a SUNDS victim, 1–3,5–9 the vast majority of cases reported were defined as autopsy-negative. 1,3,4,7–9,12–15 …”

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confidence: 99%

Does Sudden Unexplained Nocturnal Death Syndrome Remain the Autopsy-Negative Disorder: A Gross, Microscopic, and Molecular Autopsy Investigation in Southern China

Zhang

Tester

Lang

et al. 2016

Mayo Clinic Proceedings

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Objective To look for previously unrecognized cardiac structural abnormalities and address the genetic cause for sudden unexplained nocturnal death syndrome (SUNDS). Methods and Results 148 SUNDS victims and 444 controls (matched 1:3 on gender, race, and age of death within 1 year) were collected from Sun Yat-sen University from January 1, 1998 to December 31, 2014 to search morphological changes. Additional 17 Brugada syndrome (BrS) patients collected from January 1, 2006 to December 31, 2014 served as a comparative disease cohort. The Target Captured Next Generation sequencing for 80 genes associated with arrhythmia/cardiomyopathy were performed in 44 SUNDS victims and 17 BrS patients to characterize the molecular spectrum. SUNDS had slight but statistically significantly increased heart weight and valve circumference compared to controls. 12/44 SUNDS victims (SCN5A, SCN1B, CACNB2, CACNA1C, AKAP9, KCNQ1, KCNH2, KCNJ5, GATA4, NUP155, ABCC9) and 6/17 BrS patients (SCN5A, CACNA1C, P>.05) carried rare variants in primary arrhythmia-susceptibility genes. Only 2/44 SUNDS cases compared to 5/17 BrS patients hosted a rare variant in the most common BrS causing gene, SCN5A (P=.01). Using the strict American College of Medical Genetics guideline-based definition, only 2/44 (KCNQ1) SUNDS and 3/17 (SCN5A) BrS patients hosted a “(likely) pathogenic” variant. The 14/44 SUNDS cases with cardiomyopathy-related variants had a subtle but significantly decreased circumference of cardiac valves, and tended to die on average 5–6 years younger compared to the remaining 30 cases (P=.02). Conclusions We present the first comprehensive autopsy evidence that SUNDS victims may have concealed cardiac morphological changes. SUNDS and BrS may result from different molecular pathological underpinnings. The distinct association between cardiomyopathy-related rare variants and SUNDS warrants further investigation.

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Postmortem genetic screening of SNPs in RyR2 gene in sudden unexplained nocturnal death syndrome in the southern Chinese Han population

Cited by 18 publications

References 28 publications

Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population

Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population

Identification of rare variants of DSP gene in sudden unexplained nocturnal death syndrome in the southern Chinese Han population

Does Sudden Unexplained Nocturnal Death Syndrome Remain the Autopsy-Negative Disorder: A Gross, Microscopic, and Molecular Autopsy Investigation in Southern China

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