TY - JOUR
T1 - Is sudden unexplained nocturnal death syndrome in Southern China a cardiac sodium channel dysfunction disorder?
AU - Liu, Chao
AU - Tester, David J.
AU - Hou, Yiding
AU - Wang, Wen
AU - Lv, Guoli
AU - Ackerman, Michael J.
AU - Makielski, Jonathan C.
AU - Cheng, Jianding
N1 - Funding Information:
This work was supported by grants 81172901 & 81373238 (J.C.) from the National Natural Science Foundation of China , grant 11ykpy04 (to J.C.) from the Fundamental Research Funds for the Central Universities , and grant 2012BAK02B02-3 (to C.L.) from the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period.
PY - 2014/3
Y1 - 2014/3
N2 - Sudden unexplained nocturnal death syndrome (SUNDS) remains an enigma to both forensic pathologists and physicians. Previous epidemiological, clinical, and pilot genetic studies have implicated that SUNDS is most likely a disease allelic to Brugada syndrome (BrS). We have performed postmortem genetic testing to address the spectrum and role of genetic abnormalities in the SCN5A-encoded cardiac sodium channel and its several associated proteins in SUNDS victims from Southern China. Genomic DNA extracted from the blood samples of 123 medico-legal autopsy-negative SUNDS cases and 104 sex-, age- and ethnic-matched controls from Southern China underwent comprehensive amino acid coding region mutational analysis for the BrS associated genes SCN5A, SCN1B, SCN2B, SCN3B, SCN4B, MOG1, and GPD1-L using PCR and direct sequencing. We identified a total of 7 unique (4 novel) putative pathogenic mutations (all in SCN5A; V95I, R121Q [2 cases], R367H, R513H, D870H, V1764D, and S1937F) in 8/123 (6.5%) SUNDS cases. Three SCN5A mutations (V95I, R121Q, and R367H) have been previously implicated in BrS. An additional 8 cases hosted rare variants of uncertain clinical significance (SCN5A: V1098L, V1202M, R1512W; SCN1B: V138I [3 cases], T189M [2 cases]; SCN3B: A195T). There were no non-synonymous mutations found in SCN2B, SCN4B, MOG1, or GPD1-L. This first comprehensive genotyping for SCN5A and related genes in the Chinese Han population with SUNDS discovered 13 mutations, 4 of them novel, in 16 cases, which suggests cardiac sodium channel dysfunction might account for the pathogenesis of 7-13% of SUNDS in Southern China.
AB - Sudden unexplained nocturnal death syndrome (SUNDS) remains an enigma to both forensic pathologists and physicians. Previous epidemiological, clinical, and pilot genetic studies have implicated that SUNDS is most likely a disease allelic to Brugada syndrome (BrS). We have performed postmortem genetic testing to address the spectrum and role of genetic abnormalities in the SCN5A-encoded cardiac sodium channel and its several associated proteins in SUNDS victims from Southern China. Genomic DNA extracted from the blood samples of 123 medico-legal autopsy-negative SUNDS cases and 104 sex-, age- and ethnic-matched controls from Southern China underwent comprehensive amino acid coding region mutational analysis for the BrS associated genes SCN5A, SCN1B, SCN2B, SCN3B, SCN4B, MOG1, and GPD1-L using PCR and direct sequencing. We identified a total of 7 unique (4 novel) putative pathogenic mutations (all in SCN5A; V95I, R121Q [2 cases], R367H, R513H, D870H, V1764D, and S1937F) in 8/123 (6.5%) SUNDS cases. Three SCN5A mutations (V95I, R121Q, and R367H) have been previously implicated in BrS. An additional 8 cases hosted rare variants of uncertain clinical significance (SCN5A: V1098L, V1202M, R1512W; SCN1B: V138I [3 cases], T189M [2 cases]; SCN3B: A195T). There were no non-synonymous mutations found in SCN2B, SCN4B, MOG1, or GPD1-L. This first comprehensive genotyping for SCN5A and related genes in the Chinese Han population with SUNDS discovered 13 mutations, 4 of them novel, in 16 cases, which suggests cardiac sodium channel dysfunction might account for the pathogenesis of 7-13% of SUNDS in Southern China.
KW - Cardiac sodium channel β subunits
KW - GPD1-L gene
KW - MOG1 gene
KW - SCN5A gene
KW - Sudden unexplained nocturnal death syndrome (SUNDS)
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UR - http://www.scopus.com/inward/citedby.url?scp=84892659368&partnerID=8YFLogxK
U2 - 10.1016/j.forsciint.2013.12.033
DO - 10.1016/j.forsciint.2013.12.033
M3 - Article
C2 - 24529773
AN - SCOPUS:84892659368
SN - 0379-0738
VL - 236
SP - 38
EP - 45
JO - Forensic Science International
JF - Forensic Science International
ER -