Background

Sudden unexpected infant death (SUID) occurs unpredictably and remains unexplained after scene investigation and autopsy. Approximately 1 in 7 cases of SUID can be related to a cardiac cause, and developmental regulation of cardiac ion channel genes may contribute to SUID.

Objective

The goal of this study was to investigate the developmental changes in the spliceoforms of SCN5A and KCNQ1, 2 genes implicated in SUID.

Methods

Using reverse transcription quantitative real-time polymerase chain reaction, we quantified expression of SCN5A (adult and fetal) and KCNQ1 (KCNQ1a and b) spliceoforms in 153 human cardiac tissue samples from decedents that succumbed to SUID (“unexplained”) and other known causes of death (“explained noncardiac”).

Results

There is a stepwise increase in the adult/fetal SCN5A spliceoform ratio from <2 months (4.55 ± 0.36; n = 51) through infancy and into adulthood (17.41 ± 3.33; n = 5). For KCNQ1, there is a decrease in the ratio of KCNQ1b to KCNQ1a between the <2-month (0.37 ± 0.02; n = 46) and the 2- to 4-month (0.28 ± 0.02; n = 52) age groups. When broken down by sex, race, or cause of death, there were no differences in SCN5A or KCNQ1 spliceoform expression, except for a higher ratio of KCNQ1b to KCNQ1a at 5–12 months of age for SUID females (0.40 ± 0.04; n = 9) than for males (0.25 ± 0.03; n = 6) and at <2 months of age for SUID white (0.42 ± 0.03; n = 19) than for black (0.33 ± 0.05; n = 9) infants.

Conclusion

This study documents the developmental changes in SCN5A and KCNQ1 spliceoforms in humans. Our data suggest that spliceoform expression ratios change significantly throughout the first year of life.

中文翻译：

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KCNQ1 和 SCN5A 剪接形式心脏表达的发育变化：对婴儿意外死亡的影响

背景

婴儿意外猝死 (SUID) 的发生不可预测，经过现场调查和尸检仍无法解释。大约七分之一的 SUID 病例可能与心脏病有关，心脏离子通道基因的发育调节可能导致 SUID。

客观的

本研究的目的是研究SCN5A和KCNQ1这两个与 SUID 相关的基因的剪接形式的发育变化。

方法

使用逆转录定量实时聚合酶链反应，我们量化了SCN5A（成人和胎儿）和KCNQ1（KCNQ1a和b）剪接形式在 153 个死于 SUID（“不明原因”）和其他已知原因的死者心脏组织样本中的表达死亡（“解释为非心脏病”）。

结果

从 <2 个月 (4.55 ± 0.36; n = 51) 到婴儿期和成年期 (17.41 ± 3.33; n = 5)，成人/胎儿SCN5A剪接形式比率逐步增加。对于KCNQ1 ， <2 个月（0.37 ± 0.02；n = 46）和 2 至 4 个月（0.28 ± 0.02；n = 52）年龄组之间的 KCNQ1b 与 KCNQ1a比率有所下降。当按性别、种族或死因细分时， SCN5A或KCNQ1剪接形式表达没有差异，除了KCNQ1b与KCNQ1a的比率较高SUID 雌性在 5-12 个月大时（0.40 ± 0.04；n = 9）高于雄性（0.25 ± 0.03；n = 6），SUID 白种人在 <2 个月大时（0.42 ± 0.03；n = 19）比黑人 (0.33 ± 0.05; n = 9) 婴儿。

结论

本研究记录了人类SCN5A和KCNQ1剪接形式的发育变化。我们的数据表明剪接形式表达比率在生命的第一年发生显着变化。