Liebrechts-Akkerman Germaine, Liu Fan, Lao Oscar, Ooms Ariadne H A G, van Duijn Kate, Vermeulen Mark, Jaddoe Vincent W, Hofman Albert, Engelberts Adèle C, Kayser Manfred
Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
Int J Legal Med. 2014 Jul;128(4):621-9. doi: 10.1007/s00414-013-0962-0. Epub 2014 Jan 18.
Unclassified sudden infant death (USID) is the sudden and unexpected death of an infant that remains unexplained after thorough case investigation including performance of a complete autopsy and review of the circumstances of death and the clinical history. When the infant is below 1 year of age and with onset of the fatal episode apparently occurring during sleep, this is referred to as sudden infant death syndrome (SIDS). USID and SIDS remain poorly understood despite the identification of several environmental and some genetic risk factors. In this study, we investigated genetic risk factors involved in the autonomous nervous system in 195 Dutch USID/SIDS cases and 846 Dutch, age-matched healthy controls. Twenty-five DNA variants from 11 genes previously implicated in the serotonin household or in the congenital central hypoventilation syndrome, of which some have been associated with SIDS before, were tested. Of all DNA variants considered, only the length variation of the polyalanine repeat in exon 3 of the PHOX2B gene was found to be statistically significantly associated with USID/SIDS in the Dutch population after multiple test correction. Interestingly, our data suggest that contraction of the PHOX2B exon 3 polyalanine repeat that we found in six of 160 SIDS and USID cases and in six of 814 controls serves as a probable genetic risk factor for USID/SIDS at least in the Dutch population. Future studies are needed to confirm this finding and to understand the functional effect of the polyalanine repeat length variation, in particular contraction, in exon 3 of the PHOX2B gene.
未分类的婴儿猝死（USID）是指婴儿的突然意外死亡，在进行全面的病例调查（包括完整的尸检以及对死亡情况和临床病史的审查）后仍无法解释。当婴儿年龄在1岁以下且致命事件显然发生在睡眠期间时，这被称为婴儿猝死综合征（SIDS）。尽管已经确定了一些环境和一些遗传风险因素，但USID和SIDS仍然了解甚少。在本研究中，我们调查了195例荷兰USID/SIDS病例和846例年龄匹配的荷兰健康对照中涉及自主神经系统的遗传风险因素。对先前与血清素家族或先天性中枢性低通气综合征有关的11个基因中的25个DNA变异进行了检测，其中一些以前已与SIDS相关联。在所有考虑的DNA变异中，经过多重检验校正后，仅发现PHOX2B基因外显子3中多聚丙氨酸重复序列的长度变异在荷兰人群中与USID/SIDS具有统计学显著相关性。有趣的是，我们的数据表明，我们在160例SIDS和USID病例中的6例以及814例对照中的6例中发现的PHOX2B外显子3多聚丙氨酸重复序列的缩短至少在荷兰人群中是USID/SIDS的一个可能遗传风险因素。需要进一步的研究来证实这一发现，并了解PHOX2B基因外显子3中多聚丙氨酸重复序列长度变异，特别是缩短的功能影响。
