Trans-acting genetic variants causing multilocus imprinting disturbance (MLID): common mechanisms and consequences.
Trans-acting genetic variants causing multilocus imprinting disturbance (MLID): common mechanisms and consequences.
复制标题
DOI：
10.1186/s13148-022-01259-x
复制
发表时间：
2022-03-16
影响因子：
5.7
通讯作者：
Tümer Z
中科院分区：
文献类型：
--
作者：
Eggermann T;Yapici E;Bliek J;Pereda A;Begemann M;Russo S;Tannorella P;Calzari L;de Nanclares GP;Lombardi P;Temple IK;Mackay D;Riccio A;Kagami M;Ogata T;Lapunzina P;Monk D;Maher ER;Tümer Z
印迹障碍是一组以影响差异甲基化区域（DMR）的分子改变为特征的先天性疾病。迄今为止，至少有12种印迹疾病已被定义为具有重叠但可变的临床特征，包括生长和代谢紊乱、认知功能障碍、腹壁缺陷和不对称。一般来说，一个特定的DMR是在一个给定的印记疾病的个体受到影响，但有越来越多的报告与所谓的多位点印记障碍（MLID），其中异常的印记标记（最常见的甲基化损失）发生在多个DMR的个人。然而，由于文献是零散的，我们回顾了55个先前报道或新发现的MLID家族的分子和临床数据，这些家族在母体效应基因（NLRP 2，NLRP 5，NLRP 7，KHDC 3L，OOEP，PADI 6）和其他候选基因（ZFP 57，ARID 4A，ZAR 1，UHRF 1，ZNF 445）中具有推定的致病性变体。 在55个家族中，共鉴定出68种不同的候选致病性变体（NLRP 2中7种，NLRP 5中16种，NLRP 7中7种，PADI 6中17种，ZFP 57中15种，以及ARID 4A、ZAR 1、OOEP、UHRF 1、KHDC 3L和ZNF 445基因中的每一种中的单个变体）。受影响后代的临床诊断包括Beckwith-Wiedemann综合征谱系、Silver-Russell综合征谱系、短暂性新生儿糖尿病，或怀疑存在印迹障碍（未诊断）。有些家庭经常流产。 基因组母体效应和导致MLID的胎儿变体允许深入了解生命印记周期背后的机制，以及参与卵母细胞成熟和早期发育的不同因素的空间和时间功能。进一步的基础研究以及新的MLID家族的鉴定将使我们能够更好地了解不同的生殖问题之间的联系，例如母体效应变异携带者/家族中的复发性流产和先兆子痫以及非整倍体和在后代中观察到的MLID。目前的知识已经可以用于特定情况下的生殖和遗传咨询。在线版本包含补充材料，可通过10.1186/s13148-022-01259-x获得。
Imprinting disorders are a group of congenital diseases which are characterized by molecular alterations affecting differentially methylated regions (DMRs). To date, at least twelve imprinting disorders have been defined with overlapping but variable clinical features including growth and metabolic disturbances, cognitive dysfunction, abdominal wall defects and asymmetry. In general, a single specific DMR is affected in an individual with a given imprinting disorder, but there are a growing number of reports on individuals with so-called multilocus imprinting disturbances (MLID), where aberrant imprinting marks (most commonly loss of methylation) occur at multiple DMRs. However, as the literature is fragmented, we reviewed the molecular and clinical data of 55 previously reported or newly identified MLID families with putative pathogenic variants in maternal effect genes (NLRP2, NLRP5, NLRP7, KHDC3L, OOEP, PADI6) and in other candidate genes (ZFP57, ARID4A, ZAR1, UHRF1, ZNF445). In 55 families, a total of 68 different candidate pathogenic variants were identified (7 in NLRP2, 16 in NLRP5, 7 in NLRP7, 17 in PADI6, 15 in ZFP57, and a single variant in each of the genes ARID4A, ZAR1, OOEP, UHRF1, KHDC3L and ZNF445). Clinical diagnoses of affected offspring included Beckwith–Wiedemann syndrome spectrum, Silver–Russell syndrome spectrum, transient neonatal diabetes mellitus, or they were suspected for an imprinting disorder (undiagnosed). Some families had recurrent pregnancy loss. Genomic maternal effect and foetal variants causing MLID allow insights into the mechanisms behind the imprinting cycle of life, and the spatial and temporal function of the different factors involved in oocyte maturation and early development. Further basic research together with identification of new MLID families will enable a better understanding of the link between the different reproductive issues such as recurrent miscarriages and preeclampsia in maternal effect variant carriers/families and aneuploidy and the MLID observed in the offsprings. The current knowledge can already be employed in reproductive and genetic counselling in specific situations. The online version contains supplementary material available at 10.1186/s13148-022-01259-x.
登录
查看更多内容
影响因子：
4
作者：
Akoury, Elie;Gupta, Neerja;Slim, Rima
通讯作者：
Slim, Rima
影响因子：
3.5
作者：
Beygo J;Citro V;Sparago A;De Crescenzo A;Cerrato F;Heitmann M;Rademacher K;Guala A;Enklaar T;Anichini C;Cirillo Silengo M;Graf N;Prawitt D;Cubellis MV;Horsthemke B;Buiting K;Riccio A
通讯作者：
Riccio A
影响因子：
5.7
作者：
Kagami M;Hara-Isono K;Matsubara K;Nakabayashi K;Narumi S;Fukami M;Ohkubo Y;Saitsu H;Takada S;Ogata T
通讯作者：
Ogata T
影响因子：
5.7
作者：
Cubellis, Maria Vittoria;Pignata, Laura;Riccio, Andrea
通讯作者：
Riccio, Andrea
影响因子：
3.7
作者：
Azzi, Salah;Rossignol, Sylvie;Netchine, Irene
通讯作者：
Netchine, Irene