A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.
A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.
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DOI：
10.1111/cge.13189
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发表时间：
2018-04
影响因子：
3.5
通讯作者：
Stanier P
中科院分区：
文献类型：
--
作者：
Ishida M;Cullup T;Boustred C;James C;Docker J;English C;GOSgene;Lench N;Copp AJ;Moore GE;Greene NDE;Stanier P
神经管缺陷（NTD）影响大脑（无脑畸形）是致命的出生前或出生时，而较低的脊柱缺陷（脊柱裂）可能导致终身神经障碍。总的来说，NTD是世界上最常见的出生缺陷之一。这项研究的重点是无脑畸形，尽管有一个类似的频率脊柱裂，并在小鼠模型中观察到的NTD的最常见的类型，在遗传研究中有更有限的包容性。遗传的影响是强烈牵连在确定NTD的风险和分子诊断是至关重要的家庭无论是在了解的起源条件和管理未来的怀孕。在这里，我们使用了191个NTD候选基因的自定义面板，用靶向外显子组测序平台筛选了90名患有颅NTD的患者（n = 85无脑儿和n = 5颅脊柱裂）。在过滤并与我们的内部对照外显子组数据库（N = 509）进行比较后，我们确定了397种罕见变异（次要等位基因频率，MAF < 1%），其中21种以前未报告并预测具有损害性。这包括1个移码（PDGFRA），2个停止获得（MAT 1A; NOS 2）和18个错义变异。连同寡基因遗传的证据，这项研究提供了新的信息，无脑畸形的可能遗传原因。
Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in‐house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop‐gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly.
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DOI：
10.1007/s12031-012-9871-9
发表时间：
2013-03
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
De Marco P;Merello E;Consales A;Piatelli G;Cama A;Kibar Z;Capra V
通讯作者：
Capra V
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
2.7
作者：
Carroll, EA;Gerrelli, D;Klingensmith, J
通讯作者：
Klingensmith, J
影响因子：
158.5
作者：
CZEIZEL, AE;DUDAS, I
通讯作者：
DUDAS, I
DOI：
10.1038/gim.2015.60
发表时间：
2016-02
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
D'Alessandro LC;Al Turki S;Manickaraj AK;Manase D;Mulder BJ;Bergin L;Rosenberg HC;Mondal T;Gordon E;Lougheed J;Smythe J;Devriendt K;Bhattacharya S;Watkins H;Bentham J;Bowdin S;Hurles ME;Mital S
通讯作者：
Mital S