Whole exome sequencing and array-based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson-Golabi-Behmel syndrome
Whole exome sequencing and array-based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson-Golabi-Behmel syndrome
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DOI：
10.1002/pd.4920
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发表时间：
2016-10-01
影响因子：
3
通讯作者：
Gembruch, Ulrich
中科院分区：
文献类型：
--
作者：
Kehrer, Christina;Hoischen, Alexander;Gembruch, Ulrich
SGBS综合征1型和2型代表罕见的X连锁产前过度生长障碍。我们研究的目的是描述产前超声特征以及遗传work-up.MethodRetrospective分析4例产前或产后诊断SGBS在一个单一的三级转诊中心在一个为期4years.ResultsIn研究期间，4名男性胎儿与SGBS检测。在3例病例中，产前作出了最终诊断。在所有病例中，孕中期异常扫描显示左侧先天性腹股沟疝（CDH）伴其他异常; 3例SGBS 1型胎儿显示胎儿生长过度。在其中两个中，全外显子组测序分别显示基因GPC 3中可能的移码突变和点突变。在第三种情况下，多重连接依赖性探针扩增（MLPA）揭示了基因GPC 3中外显子3-7的半合子重复。羊水细胞的阵列比较基因组杂交（CGH）显示OFD 1基因缺失，证实第4例为SGBS 2型。结论我们可以证明，在存在CDH的情况下，胎儿综合征可以通过详细的超声检查，然后使用微阵列技术和全外显子组测序进行选择性和分级的分子诊断来区分。(c)2016约翰威利父子有限公司
ObjectiveSimpson-Golabi-Behmel (SGBS) syndrome type 1 and type 2 represent rare X-linked prenatal overgrowth disorders. The aim of our study is to describe the prenatal sonographic features as well as the genetic work-up.MethodRetrospective analysis of four cases with a pre- or postnatal diagnosis of SGBS in a single tertiary referral center within a period of 4years.ResultsIn the study period, four male fetuses with SGBS were detected. The final diagnosis was made prenatally in three cases. In all cases the second trimester anomaly scan revealed left sided congenital diaphragmatic hernia (CDH) with additional anomalies; three fetuses with SGBS type 1 showed fetal overgrowth. In two of these, whole exome sequencing showed a possible frameshift mutation and a point mutation in the gene GPC3, respectively. In the third case, multiplex ligation-dependent probe amplification (MLPA) revealed a hemizygous duplication of exon 3-7 in the gene GPC3. In the fourth case, SGBS type 2 was confirmed by array comparative genomic hybridization (CGH) of amniotic fluid cells showing a deletion of the gene OFD1.ConclusionWe could demonstrate, that in the presence of a CDH, syndromes of the fetus can be increasingly differentiated by detailed sonography followed by a selective and graded molecular diagnostic using microarray techniques and whole exome sequencing. (c) 2016 John Wiley & Sons, Ltd.