High diagnosis rate for nonimmune hydrops fetalis with prenatal clinical exome from the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study
High diagnosis rate for nonimmune hydrops fetalis with prenatal clinical exome from the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study
复制标题
DOI：
10.1038/s41436-021-01121-0
复制
发表时间：
2021-03-08
影响因子：
8.8
通讯作者：
Berger, Seth I.
中科院分区：
文献类型：
--
作者：
Al-Kouatly, Huda B.;Makhamreh, Mona M.;Berger, Seth I.
目的非免疫性积水胎儿（NIHF）表现为危及生命的多胎室积液，可由遗传和非遗传病因引起。我们探讨了产前外显子组测序（ES）检测NIHF阴性标准NIHF检查后的增量诊断率。方法：参加产前测序诊断结果（HYDROPS）研究的参与者符合NIHF的严格定义，并且有阴性的标准护理检查。胎儿样本和父母血液的临床三组ES在clia认证的参考实验室进行，由遗传学家和遗传咨询师返回临床报告。阴性外显子组与随后的超声和记录信息一起重新分析。结果22个胎儿外显子组报告11例（50%）诊断结果，5例（22.7%）可能诊断。诊断病例包括7例新显性疾病、3例隐性疾病和1例遗传性显性疾病，包括4例努南综合征（PTPN11、RAF1、RIT1和RRAS2）、3例肌肉骨骼疾病（RYR1、AMER1和BICD2）、2例代谢疾病（唾液中毒和多种硫酸盐酶缺乏症）、1例Kabuki综合征和1例先天性贫血（KLF1）。结论NIHF的病因可预测产后预后及今后妊娠的复发风险。ES在标准治疗测试后为NIHF提供了较高的增量诊断率，应在检查中予以考虑。
Purpose Nonimmune hydrops fetalis (NIHF) presents as life-threatening fluid collections in multiple fetal compartments and can be caused by both genetic and non-genetic etiologies. We explored incremental diagnostic yield of testing with prenatal exome sequencing (ES) for NIHF following a negative standard NIHF workup. Methods Participants enrolled into the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) study met a strict definition of NIHF and had negative standard-of-care workup. Clinical trio ES from fetal samples and parental blood was performed at a CLIA-certified reference laboratory with clinical reports returned by geneticists and genetic counselors. Negative exomes were reanalyzed with information from subsequent ultrasounds and records. Results Twenty-two fetal exomes reported 11 (50%) diagnostic results and five possible diagnoses (22.7%). Diagnosed cases comprised seven de novodominant disorders, three recessive disorders, and one inherited dominant disorder including four Noonan syndromes (PTPN11, RAF1, RIT1, and RRAS2), three musculoskeletal disorders (RYR1, AMER1, and BICD2), two metabolic disorders (sialidosis and multiple sulfatase deficiency), one Kabuki syndrome, and one congenital anemia (KLF1). Conclusion The etiology of NIHF predicts postnatal prognosis and recurrence risk in future pregnancies. ES provides high incremental diagnostic yield for NIHF after standard-of-care testing and should be considered in the workup.