Diagnostic yield using whole-genome sequencing and in-silico panel of 281 genes associated with non-immune hydrops fetalis in clinical setting.
Diagnostic yield using whole-genome sequencing and in-silico panel of 281 genes associated with non-immune hydrops fetalis in clinical setting.
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在临床环境中，使用全基因组测序和 281 个与非免疫性胎儿水肿相关基因的计算机模拟面板进行诊断。
DOI：
10.1002/uog.24911
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发表时间：
2022-10
影响因子：
7.1
通讯作者：
Iwarsson, E.
中科院分区：
文献类型：
--
作者：
Westenius, E.;Sahlin, E.;Conner, P.;Lindstrand, A.;Iwarsson, E.
研究临床全基因组测序（WGS）在产前诊断的非免疫性水肿胎儿（NIHF）中的诊断率。这是一项对23例产前诊断为NIHF的胎儿进行的回顾性研究，三体和拷贝数变异阴性，由WGS使用与胎儿水肿相关的281个基因的计算机模拟面板进行分析。由于在主要队列中鉴定出高比例的HRAS基因致病性变体，因此在一个复制队列中进行了HRAS的桑格测序，该队列由另外24例三体性和拷贝数变体阴性且未接受WGS的NIHF胎儿组成。在主要队列的23例胎儿中，12例（52.2%）实现了分子诊断。在7个基因中鉴定出致病性或可能致病性变体：HRAS（n = 5）、RIT 1（n = 2）、FOXP 3（n = 1）、GLB 1（n = 1）、MAP 2K 1（n = 1）、PTPN 11（n = 1）和RASA 1（n = 1）。12种致病变异的遗传模式为10例常染色体显性（HRAS、MAP 2K 1、PTPN 11、RASA 1、RIT 1），1例常染色体隐性（GLB 1）和1例X连锁隐性（FOXP 3）。在复制队列的24个胎儿中，在一个中鉴定出HRAS的致病性变体，导致我们的两个队列中致病性HRAS变体的总频率为12.8%（6/47）。我们使用281个基因的计算机模拟面板证明了NIHF中临床WGS的诊断率为52%。然而，高诊断率可能归因于样本量小和纳入胎儿中重度表型的可能过度表达。考虑到我们的队列中排除了染色体异常，当WGS分析包括染色体畸变时，产前诊断的NIHF的检出率可能高达75%。版权所有© 2022作者。妇产科超声由John Wiley & Sons Ltd代表国际妇产科超声学会出版。链接文章：这篇文章有林和李的评论。点击这里查看通讯。本文摘要已被翻译成西班牙语和中文。按照摘要中的链接查看翻译。
To investigate the diagnostic yield of clinical whole‐genome sequencing (WGS) in prenatally diagnosed non‐immune hydrops fetalis (NIHF). This was a retrospective study of 23 fetuses with prenatally diagnosed NIHF, negative for trisomies and copy‐number variants, referred for analysis by WGS with an in‐silico panel of 281 genes associated with hydrops fetalis. Due to identification of a high proportion of causative variants in the HRAS gene in the main cohort, Sanger sequencing of HRAS was performed in a replication cohort, consisting of 24 additional fetuses with NIHF that were negative for trisomies and copy‐number variants and had not undergone WGS. Of the 23 fetuses in the main cohort, a molecular diagnosis was achieved in 12 (52.2%). Pathogenic or likely pathogenic variants were identified in seven genes: HRAS (n = 5), RIT1 (n = 2), FOXP3 (n = 1), GLB1 (n = 1), MAP2K1 (n = 1), PTPN11 (n = 1) and RASA1 (n = 1). The inheritance pattern of the 12 causative variants was autosomal dominant in 10 cases (HRAS, MAP2K1, PTPN11, RASA1, RIT1), autosomal recessive in one (GLB1) and X‐linked recessive in one (FOXP3). Of the 24 fetuses in the replication cohort, a pathogenic variant in HRAS was identified in one, resulting in an overall frequency of causative HRAS variants of 12.8% (6/47) in our two cohorts. We demonstrate a diagnostic yield of 52% with clinical WGS in NIHF using an in‐silico panel of 281 genes. However, the high diagnostic yield may be attributed to the small sample size and possible over‐representation of severe phenotypes in the included fetuses. Bearing in mind that chromosomal abnormalities were excluded in our cohorts, a detection rate of up to 75% is possible in prenatally diagnosed NIHF when WGS analysis includes calling of chromosomal aberrations. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Lin and Li. Click here to view the Correspondence. This article's abstract has been translated into Spanish and Chinese. Follow the links from the abstract to view the translations.
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影响因子：
12.3
作者：
Stranneheim H;Lagerstedt-Robinson K;Magnusson M;Kvarnung M;Nilsson D;Lesko N;Engvall M;Anderlid BM;Arnell H;Johansson CB;Barbaro M;Björck E;Bruhn H;Eisfeldt J;Freyer C;Grigelioniene G;Gustavsson P;Hammarsjö A;Hellström-Pigg M;Iwarsson E;Jemt A;Laaksonen M;Enoksson SL;Malmgren H;Naess K;Nordenskjöld M;Oscarson M;Pettersson M;Rasi C;Rosenbaum A;Sahlin E;Sardh E;Stödberg T;Tesi B;Tham E;Thonberg H;Töhönen V;von Döbeln U;Vassiliou D;Vonlanthen S;Wikström AC;Wincent J;Winqvist O;Wredenberg A;Ygberg S;Zetterström RH;Marits P;Soller MJ;Nordgren A;Wirta V;Lindstrand A;Wedell A
通讯作者：
Wedell A
影响因子：
3
作者：
Shaffer, Lisa G.;Rosenfeld, Jill A.;Dabell, Mindy P.;Coppinger, Justine;Bandholz, Anne M.;Ellison, Jayw.;Ravnan, J. Britt;Torchia, Beth S.;Ballif, Blake C.;Fisher, Allan J.
通讯作者：
Fisher, Allan J.
影响因子：
3
作者：
Santo, Susana;Mansour, Sahar;Bhide, Amar
通讯作者：
Bhide, Amar
影响因子：
12.3
作者：
Lindstrand, Anna;Eisfeldt, Jesper;Nilsson, Daniel
通讯作者：
Nilsson, Daniel
影响因子：
1.6
作者：
Ota, Shiyo;Sahara, Jun;Mitsuda, Nobuaki
通讯作者：
Mitsuda, Nobuaki