Genomic sequencing has a high diagnostic yield in children with congenital anomalies of the heart and urinary system.
Genomic sequencing has a high diagnostic yield in children with congenital anomalies of the heart and urinary system.
复制标题
DOI：
10.3389/fped.2023.1157630
复制
发表时间：
2023
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
--
作者：
先天性心脏病（CHD）和先天性肾脏和泌尿道畸形（CAKUT）是儿童期发病率和死亡率较高的原因。在每个器官系统中，已经确定了数十种异常的单基因原因。然而，尽管30%的CHD患者也有CAKUT，并且两个器官都来自外侧中胚层，但这些器官系统的先天性异常中涉及的基因很少重叠。我们试图确定CAKUT和CHD患者是否具有单基因病因，长期目标是指导未来的诊断工作和改善结果。回顾性审查电子病历（EMR），确定2015年1月至2020年7月期间在Rady儿童医院住院的CAKUT和CHD患者，他们接受了全外显子组测序（WES）或全基因组测序（WGS）。收集的数据包括人口统计学、表现型、遗传结果和母亲的妊娠史。对WGS数据进行了重新分析，特别关注CAKUT和CHD表型。遗传学结果进行了审查，以确定CAKUT和CHD表型的致病基因，候选基因和新基因。识别并分类了相关的其他结构畸形。确定了32名患者。8例患者有CAKUT/CHD表型的致病变异，3例患者有候选变异，3例患者有潜在的新变异。5例患者有与CAKUT/CHD表型无关的基因变异，13例患者没有发现变异。其中，8例患者被确定为CHD/CAKUT表型的可能替代原因。88%的CAKUT/CHD患者至少有一个额外的器官系统存在结构畸形。总的来说，我们的研究表明，在住院的冠心病和CAKUT患者中，单基因病因的发生率很高，诊断率为44%。因此，医生应该高度怀疑这一人群中的遗传病。总之，这些数据提供了关于如何接近患有CAKUT和CHD的急性病患者的有价值的信息，包括指导相关表型的诊断工作，以及对住院儿童中CAKUT和CHD重叠综合征的遗传学的新见解。
Congenital heart defects (CHD) and congenital anomalies of the kidney and urinary tract (CAKUT) account for significant morbidity and mortality in childhood. Dozens of monogenic causes of anomalies in each organ system have been identified. However, even though 30% of CHD patients also have a CAKUT and both organs arise from the lateral mesoderm, there is sparse overlap of the genes implicated in the congenital anomalies for these organ systems. We sought to determine whether patients with both CAKUT and CHD have a monogenic etiology, with the long-term goal of guiding future diagnostic work up and improving outcomes. Retrospective review of electronic medical records (EMR), identifying patients admitted to Rady Children's Hospital between January 2015 and July 2020 with both CAKUT and CHD who underwent either whole exome sequencing (WES) or whole genome sequencing (WGS). Data collected included demographics, presenting phenotype, genetic results, and mother's pregnancy history. WGS data was reanalyzed with a specific focus on the CAKUT and CHD phenotype. Genetic results were reviewed to identify causative, candidate, and novel genes for the CAKUT and CHD phenotype. Associated additional structural malformations were identified and categorized. Thirty-two patients were identified. Eight patients had causative variants for the CAKUT/CHD phenotype, three patients had candidate variants, and three patients had potential novel variants. Five patients had variants in genes not associated with the CAKUT/CHD phenotype, and 13 patients had no variant identified. Of these, eight patients were identified as having possible alternative causes for their CHD/CAKUT phenotype. Eighty-eight percent of all CAKUT/CHD patients had at least one additional organ system with a structural malformation. Overall, our study demonstrated a high rate of monogenic etiologies in hospitalized patients with both CHD and CAKUT, with a diagnostic rate of 44%. Thus, physicians should have a high suspicion for genetic disease in this population. Together, these data provide valuable information on how to approach acutely ill patients with CAKUT and CHD, including guiding diagnostic work up for associated phenotypes, as well as novel insights into the genetics of CAKUT and CHD overlap syndromes in hospitalized children.
登录
查看更多内容
影响因子：
1.3
作者：
Smith, Jodi M.;Stablein, Donald M.;McDonald, Ruth A.
通讯作者：
McDonald, Ruth A.
影响因子：
9.8
作者：
De Tomasi, Lara;David, Pierre;Jeanpierre, Cecile
通讯作者：
Jeanpierre, Cecile
影响因子：
3.5
作者：
Alagramam, KN;Yuan, HJ;Smith, RJH
通讯作者：
Smith, RJH
影响因子：
9.8
作者：
Seu, Katie G.;Trump, Lisa R.;Kalfa, Theodosia A.
通讯作者：
Kalfa, Theodosia A.
DOI：
10.1038/s41431-020-00713-9
发表时间：
2021-01
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Bertoli-Avella AM;Beetz C;Ameziane N;Rocha ME;Guatibonza P;Pereira C;Calvo M;Herrera-Ordonez N;Segura-Castel M;Diego-Alvarez D;Zawada M;Kandaswamy KK;Werber M;Paknia O;Zielske S;Ugrinovski D;Warnack G;Kampe K;Iurașcu MI;Cozma C;Vogel F;Alhashem A;Hertecant J;Al-Shamsi AM;Alswaid AF;Eyaid W;Al Mutairi F;Alfares A;Albalwi MA;Alfadhel M;Al-Sannaa NA;Reardon W;Alanay Y;Rolfs A;Bauer P
通讯作者：
Bauer P