Robert's Program on Sudden Death in Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Epilepsia. 2018 Apr;59(4):e56-e62. doi: 10.1111/epi.14055. Epub 2018 Mar 30.
We identified SCN1A variants in 2 infants who died of sudden infant death syndrome (SIDS) with hippocampal abnormalities from an exome sequencing study of 10 cases of SIDS but no history of seizures. One harbored SCN1A G682V, and the other had 2 SCN1A variants in cis: L1296M and E1308D, a variant previously associated with epilepsy. Functional evaluation in a heterologous expression system demonstrated partial loss of function for both G682V and the compound variant L1296M/E1308D. Our cases represent a novel association between SCN1A and SIDS, extending the SCN1A spectrum from epilepsy to SIDS. Our findings provide insights into SIDS and support genetic evaluation focused on epilepsy genes in SIDS.
我们从 10 例无癫痫发作史的 SIDS 病例的外显子组测序研究中发现了 2 例死于伴有海马异常的婴儿猝死综合征（SIDS）的婴儿的 SCN1A 变异体。其中一个携带 SCN1A G682V，另一个则携带 2 个 SCN1A 顺式变异体：L1296M 和 E1308D，该变异体先前与癫痫有关。在异源表达系统中的功能评估表明，G682V 和复合变异体 L1296M/E1308D 均存在部分功能丧失。我们的病例代表了 SCN1A 与 SIDS 之间的新关联，将 SCN1A 的范围从癫痫扩展到 SIDS。我们的发现为 SIDS 提供了新的见解，并支持针对 SIDS 中癫痫基因的遗传评估。
