Diagnosis of Chronic Intestinal Pseudo-obstruction and Megacystis by Sequencing the ACTG2 Gene.
Diagnosis of Chronic Intestinal Pseudo-obstruction and Megacystis by Sequencing the ACTG2 Gene.
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DOI：
10.1097/mpg.0000000000001608
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发表时间：
2017-10
影响因子：
2.9
通讯作者：
Milunsky J
中科院分区：
文献类型：
--
作者：
Milunsky A;Baldwin C;Zhang X;Primack D;Curnow A;Milunsky J
慢性假性肠梗阻(CIPO)的诊断依赖于临床特征、测压和影像检查。本报告旨在确定ACTG2基因测序在诊断中的作用。此外，我们的目标是确定在我们随机收集的先证者队列和之前发表的先证者中发现突变的频率。对4例CIPO先证者进行了外显子全序列测定。随后，在另外24个先证者(总共28个)中仅对ACTG2基因进行了测序。我们分析了83名先证者和我们的28名先证者[总计111名]的公开数据，并确定了有多少先证者具有致病变异和确切的基因型别。全外显子组和Sanger测序显示，4/28的先证者和83个已发表的先证者中的45人[49/111(44.1%)]发现ACTG2基因存在致病变异。此外，还发现了ACTG2基因的突变热点。遗传异质性很明显。来自111个家系中每一个个体的联合基因测序结果使49个(44%)的ACTG2突变得到了准确的诊断。及早确认运动障碍对患者和家属的好处不仅有助于避免不必要的干预，而且能够制定适当的治疗办法，避免营养不良和生长不良等继发性疾病。了解父母的致病变异，有50%的复发风险，为遗传咨询提供了机会。
The diagnosis of chronic intestinal pseudo-obstruction (CIPO) has depended on clinical features, manometry, and imaging. This report aimed to determine the efficacy of sequencing the ACTG2 gene for diagnosis. In addition, the goal was to determine how often a mutation would be found in our randomly collected cohort of probands and those probands published previously. Whole exome sequencing was performed in 4 probands with CIPO. Subsequently, only the ACTG2 gene was sequenced in another 24 probands (total 28). We analyzed published data of 83 probands plus our 28 [total 111] and determined how many had pathogenic variants and the precise genotype. Whole exome and Sanger sequencing revealed a pathogenic variant in the ACTG2 gene in 4/28 of our probands and in 45 out of 83 published probands [49/111(44.1%)]. Moreover, a mutational hotspot in the ACTG2 gene was recognized. Genetic heterogeneity is evident. Pooled gene sequencing results from one individual in each of 111 families enabled a precise diagnosis of an ACTG2 mutation in 49 (44%). The benefit to patients and families of early confirmation of a motility disorder not only helps avoid unnecessary intervention, but also enables institution of appropriate treatments and avoidance of secondary disorders such as malnutrition and poor growth. Knowledge of a pathogenic variant in a parent, with a 50% risk of recurrence, provides an opportunity for genetic counseling.