Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans.
Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans.
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NLRP5中的突变与人类的生殖浪费和多焦点疾病有关。
DOI：
10.1038/ncomms9086
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发表时间：
2015-09-01
影响因子：
16.6
通讯作者：
Mackay DJ
中科院分区：
文献类型：
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作者：
Docherty LE;Rezwan FI;Poole RL;Turner CL;Kivuva E;Maher ER;Smithson SF;Hamilton-Shield JP;Patalan M;Gizewska M;Peregud-Pogorzelski J;Beygo J;Buiting K;Horsthemke B;Soellner L;Begemann M;Eggermann T;Baple E;Mansour S;Temple IK;Mackay DJ
人类印迹疾病是指与基因组中印迹基因位点的双亲特异性DNA甲基化异常有关的生长、发育和代谢的先天性疾病。一些印迹疾病有较高的患病率比预期的单卵双胞胎，辅助生殖技术的父母之间，和干扰的多个印迹基因座，很少有致病性的反式作用mutations已经found.In这里，我们报告突变NLRP 5在5个母亲的个人受到多位点印迹干扰。其他人类NLRP基因，NLRP 7和NLRP 2的母源效应突变分别引起家族性双亲葡萄胎和多位点印迹障碍。NLRP5突变的母亲的后代具有异质性临床和表观遗传特征，但病例包括不一致的单卵双胞胎，特发性发育迟缓和自闭症的个体，以及受不孕症和生殖浪费影响的家庭。NLRP5突变表明母体生殖适应性、早期合子发育和基因组印记之间存在联系。基因组印记障碍可引起影响生长、代谢和行为的复杂先天性疾病。在这里，作者报告了NLRP 5的突变，这表明印记，母体生殖适应性和合子发育之间的联系。
Human-imprinting disorders are congenital disorders of growth, development and metabolism, associated with disturbance of parent of origin-specific DNA methylation at imprinted loci across the genome. Some imprinting disorders have higher than expected prevalence of monozygotic twinning, of assisted reproductive technology among parents, and of disturbance of multiple imprinted loci, for which few causative trans-acting mutations have been found. Here we report mutations in NLRP5 in five mothers of individuals affected by multilocus imprinting disturbance. Maternal-effect mutations of other human NLRP genes, NLRP7 and NLRP2, cause familial biparental hydatidiform mole and multilocus imprinting disturbance, respectively. Offspring of mothers with NLRP5 mutations have heterogenous clinical and epigenetic features, but cases include a discordant monozygotic twin pair, individuals with idiopathic developmental delay and autism, and families affected by infertility and reproductive wastage. NLRP5 mutations suggest connections between maternal reproductive fitness, early zygotic development and genomic imprinting. Genomic imprinting disturbance can give rise to complex congenital disorders affecting growth, metabolism and behaviour. Here the authors report mutations in NLRP5, which suggests a connection between imprinting, maternal reproductive fitness and zygotic development.