The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies.
The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies.
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靶向基因组捕获和大规模并行测序在中国白质脑病诊断中的应用
DOI：
10.1038/srep35936
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发表时间：
2016-10-25
影响因子：
4.6
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Wang X;He F;Yin F;Chen C;Wu L;Yang L;Peng J
白质脑病是具有高度临床异质性的疾病。在临床工作中，医生很难做出明确的病因诊断。在这里，我们设计了一个包含已知与白质脑病相关的致病基因的定制探针库，对49例以脑白质损伤为主要影像学改变的中国患者进行了靶向基因捕获和大规模并行测序（MPS），并通过桑格测序对先证者的父母进行了验证。结果，总共 40.8% (20/49) 的患者确定了致病性突变，其中 4 例与异染性脑白质营养不良相关，3 例与消失性白质脑白质病相关，3 例与线粒体复合物 I 缺陷相关，1 例与球状细胞脑白质营养不良（或克拉伯病）相关，3 例与伴有皮质下囊肿的巨脑白质脑病相关，2 例与皮质下囊肿相关。 Pelizaeus-Merzbacher 病，两种与 X 连锁肾上腺脑白质营养不良相关，一种与 Zellweger 综合征相关，一种与亚历山大病相关。靶向捕获和 MPS 能够识别导致白质脑病的所有类别的突变。我们的研究将靶向捕获和 MPS 技术与临床和基因诊断相结合，并强调了其在临床环境中快速、全面的基因检测的有用性。这种方法还将扩大我们对白质脑病的遗传和临床谱的了解。
Leukoencephalopathies are diseases with high clinical heterogeneity. In clinical work, it’s difficult for doctors to make a definite etiological diagnosis. Here, we designed a custom probe library which contains the known pathogenic genes reported to be associated with Leukoencephalopathies, and performed targeted gene capture and massively parallel sequencing (MPS) among 49 Chinese patients who has white matter damage as the main imaging changes, and made the validation by Sanger sequencing for the probands’ parents. As result, a total of 40.8% (20/49) of the patients identified pathogenic mutations, including four associated with metachromatic leukodystrophy, three associated with vanishing white matter leukoencephalopathy, three associated with mitochondrial complex I deficiency, one associated with Globoid cell leukodystrophy (or Krabbe diseases), three associated with megalencephalic leukoencephalopathy with subcortical cysts, two associated with Pelizaeus-Merzbacher disease, two associated with X-linked adrenoleukodystrophy, one associated with Zellweger syndrome and one associated with Alexander disease. Targeted capture and MPS enables to identify mutations of all classes causing leukoencephalopathy. Our study combines targeted capture and MPS technology with clinical and genetic diagnosis and highlights its usefulness for rapid and comprehensive genetic testing in the clinical setting. This method will also expand our knowledge of the genetic and clinical spectra of leukoencephalopathy.
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影响因子：
29
作者：
Kremer S;Renard F;Achard S;Lana-Peixoto MA;Palace J;Asgari N;Klawiter EC;Tenembaum SN;Banwell B;Greenberg BM;Bennett JL;Levy M;Villoslada P;Saiz A;Fujihara K;Chan KH;Schippling S;Paul F;Kim HJ;de Seze J;Wuerfel JT;Guthy-Jackson Charitable Foundation (GJCF) Neuromyelitis Optica (NMO) International Clinical Consortium and Biorepository;Cabre P;Marignier R;Tedder T;van Pelt D;Broadley S;Chitnis T;Wingerchuk D;Pandit L;Leite MI;Apiwattanakul M;Kleiter I;Prayoonwiwat N;Han M;Hellwig K;van Herle K;John G;Hooper DC;Nakashima I;Sato D;Yeaman MR;Waubant E;Zamvil S;Stüve O;Aktas O;Smith TJ;Jacob A;O'Connor K
通讯作者：
O'Connor K
影响因子：
6.6
作者：
Sakr RA;Schizas M;Carniello JV;Ng CK;Piscuoglio S;Giri D;Andrade VP;De Brot M;Lim RS;Towers R;Weigelt B;Reis-Filho JS;King TA
通讯作者：
King TA
影响因子：
9.9
作者：
Schiffmann, Raphael;van der Knaap, Marjo S.
通讯作者：
van der Knaap, Marjo S.
影响因子：
2.7
作者：
Gordon, Hannah B.;Letsou, Anthea;Bonkowsky, Joshua L.
通讯作者：
Bonkowsky, Joshua L.
影响因子：
3.5
作者：
Grad, LI;Lemire, BD
通讯作者：
Lemire, BD