Application of Next-Generation Sequencing for Genetic Diagnosis in Neonatal Intensive Care Units: Results of a Multicenter Study in China.
Application of Next-Generation Sequencing for Genetic Diagnosis in Neonatal Intensive Care Units: Results of a Multicenter Study in China.
复制标题
新一代测序在新生儿重症监护病房基因诊断中的应用：中国多中心研究结果
DOI：
10.3389/fgene.2020.565078
复制
发表时间：
2020
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Zhu T;Gong X;Bei F;Ma L;Chen Y;Zhang Y;Wang X;Sun J;Wang J;Qiu G;Sun J;Sun Y;Zhang Y
为了确定下一代测序（NGS）的临床可用性，并为年龄小于100天且疑似患有遗传异质性疾病的危重婴儿提出标准诊断程序，于2016年1月至2018年12月在中国上海三家三级医院的新生儿重症监护室（NICU）进行了一项回顾性研究。对307名患者进行了全外显子组测序（WES）或面板测序。Trio-WES、trio-panel、先证者-WES和先证者-panel的诊断率分别为39.71%（83/209）、68.75%（22/32）、59.09%（26/44）和33.33%（4/12）。对142例（46.25%）婴儿进行了连续性分子诊断，共发现99种疾病，其中21种疾病占诊断病例的44.37%。61.73%（50/81）的死亡婴儿被确定为遗传病因。三分之一（29.58%）的诊断婴儿具有以下四种临床特征之一，其诊断率较高：（校正比值比[aOR]，19.7; 95%置信区间[CI]，2.5-156.3），复杂免疫相关表型（aOR，9.2; 95%CI，1.4-83.5），混合神经系统表型和先天性异常（aOR，5.0; 95%CI，1.3-19.1），或混合代谢和神经系统表型（aOR，4.5; 95%CI，1.0-21.5）。我们的研究结果表明，NGS是一种有效的诊断工具。表现出皮肤、复杂的免疫相关疾病、代谢和神经症状的婴儿携带已知致病基因变异的可能性更高。特异性表型的数量可以作为阳性分子诊断的独立预测因子，而不是孤立的异常。我们开发了一种基于个体特征的分子诊断程序，用于NGS在中国NICU人群中的诊断。
To identify next-generation-sequencing (NGS) clinical usability and to propose a standard diagnostic routine for critically ill infants, aged less than 100 days and suspected of having a genetically heterogeneous condition, a retrospective study was conducted between January 2016 and December 2018 at neonatal intensive care units (NICUs) of three tertiary hospitals in Shanghai, China. Whole-exome sequencing (WES) or panel sequencing was performed on 307 patients. Trio-WES, trio-panel, proband-WES, and proband-panel diagnostic yields were 39.71% (83/209), 68.75% (22/32), 59.09% (26/44), and 33.33% (4/12), respectively. Definitive molecular diagnoses of 142 infants (46.25%) uncovered 99 disorders; 21 disorders displayed on 44.37% of the diagnosed patients. Genetic etiologies were identified for 61.73% (50/81) of the deceased infants. One in three (29.58%) diagnosed infants exhibited one of the following four clinical traits which had a higher odds of diagnostic rate: integument abnormality (adjusted odds ratio [aOR], 19.7; 95% confidence interval [CI], 2.5–156.3), complex immune-related phenotypes (aOR, 9.2; 95% CI, 1.4–83.5), mixed nervous system phenotypes and congenital anomalies (aOR, 5.0; 95% CI, 1.3–19.1), or mixed metabolism and nervous system phenotypes (aOR, 4.5; 95% CI, 1.0–21.5). Our results demonstrated that NGS was an effective diagnostic tool. Infants exhibiting integument, complex immune-related conditions, metabolism, and nervous signs have higher chances of carrying variants in known disease-causing genes. The number of specific phenotypes could be used as an independent predictor of a positive molecular diagnosis, rather than an isolated abnormality. We developed a molecular diagnostic procedure for the use of NGS for diagnosis in Chinese NICU population based on individual characteristics.
登录
查看更多内容
影响因子：
4.1
作者：
Fernandez-Marmiesse A;Gouveia S;Couce ML
通讯作者：
Couce ML
影响因子：
14.9
作者：
Köhler S;Vasilevsky NA;Engelstad M;Foster E;McMurry J;Aymé S;Baynam G;Bello SM;Boerkoel CF;Boycott KM;Brudno M;Buske OJ;Chinnery PF;Cipriani V;Connell LE;Dawkins HJ;DeMare LE;Devereau AD;de Vries BB;Firth HV;Freson K;Greene D;Hamosh A;Helbig I;Hum C;Jähn JA;James R;Krause R;F Laulederkind SJ;Lochmüller H;Lyon GJ;Ogishima S;Olry A;Ouwehand WH;Pontikos N;Rath A;Schaefer F;Scott RH;Segal M;Sergouniotis PI;Sever R;Smith CL;Straub V;Thompson R;Turner C;Turro E;Veltman MW;Vulliamy T;Yu J;von Ziegenweidt J;Zankl A;Züchner S;Zemojtel T;Jacobsen JO;Groza T;Smedley D;Mungall CJ;Haendel M;Robinson PN
通讯作者：
Robinson PN
影响因子：
8
作者：
Gyngell, Christopher;Newson, Ainsley J.;Savulescu, Julian
通讯作者：
Savulescu, Julian
DOI：
10.1136/archdischild-2015-308568
发表时间：
2016-03
期刊：
Archives of disease in childhood. Fetal and neonatal edition
影响因子：
--
作者：
Wilkinson DJ;Barnett C;Savulescu J;Newson AJ
通讯作者：
Newson AJ
临床外显子组测序：2819个样品的结果反映了1000个家庭。
DOI：
10.1038/ejhg.2016.146
发表时间：
2017-02
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Trujillano D;Bertoli-Avella AM;Kumar Kandaswamy K;Weiss ME;Köster J;Marais A;Paknia O;Schröder R;Garcia-Aznar JM;Werber M;Brandau O;Calvo Del Castillo M;Baldi C;Wessel K;Kishore S;Nahavandi N;Eyaid W;Al Rifai MT;Al-Rumayyan A;Al-Twaijri W;Alothaim A;Alhashem A;Al-Sannaa N;Al-Balwi M;Alfadhel M;Rolfs A;Abou Jamra R
通讯作者：
Abou Jamra R