Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings
Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings
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DOI：
10.1038/ejhg.2012.285
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发表时间：
2013-09-01
影响因子：
5.2
通讯作者：
Yntema, Helger G.
中科院分区：
文献类型：
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作者：
Croonen, Ellen A.;Nillesen, Willy M.;Yntema, Helger G.
在最近的研究中，努南综合征（NS）的胎儿与增加项透明性（NT）和正常核型的产前检测，突变已报告在9-16%的情况下。在这项研究中，75个胎儿的DNA正常核型和异常的超声检查结果进行了测试，在诊断设置的突变（一个子集）的四个最常见的突变NS基因。在13个胎儿（17.3%）中检测到PTPN 11、KRAS或RAF 1的从头突变。超声检查结果包括NT增加、颈静脉淋巴囊（JLS）扩张、胸腔积液、肾脏异常、羊水过多、囊性水瘤、心脏异常、胎儿水肿和腹水。第二组由60个超声异常胎儿的匿名DNA组成，检测了10个NS基因的突变。在该组中，已经鉴定了五种可能的致病性突变（在PTPN 11（n = 2）、RAF 1、BRAF和MAP 2K 1（各n = 1）中）。我们建议在NT增加且至少有以下一种额外特征的妊娠中进行PTPN 11，KRAS和RAF 1的产前检测：羊水过多，胎儿水肿，肾脏异常，JLS扩张，胸腔积液，心脏异常，囊性水瘤和腹水。如果可能，应考虑BRAF和MAP 2K 1的突变分析。
In recent studies on prenatal testing for Noonan syndrome (NS) in fetuses with an increased nuchal translucency (NT) and a normal karyotype, mutations have been reported in 9-16% of cases. In this study, DNA of 75 fetuses with a normal karyotype and abnormal ultrasound findings was tested in a diagnostic setting for mutations in (a subset of) the four most commonly mutated NS genes. A de novo mutation in either PTPN11, KRAS or RAF1 was detected in 13 fetuses (17.3%). Ultrasound findings were increased NT, distended jugular lymphatic sacs (JLS), hydrothorax, renal anomalies, polyhydramnios, cystic hygroma, cardiac anomalies, hydrops fetalis and ascites. A second group, consisting of anonymized DNA of 60 other fetuses with sonographic abnormalities, was tested for mutations in 10 NS genes. In this group, five possible pathogenic mutations have been identified (in PTPN11 (n = 2), RAF1, BRAF and MAP2K1 (each n = 1)). We recommend prenatal testing of PTPN11, KRAS and RAF1 in pregnancies with an increased NT and at least one of the following additional features: polyhydramnios, hydrops fetalis, renal anomalies, distended JLS, hydrothorax, cardiac anomalies, cystic hygroma and ascites. If possible, mutation analysis of BRAF and MAP2K1 should be considered.