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首页> 外文期刊>The Journal of molecular diagnostics: JMD >Addition of H19 'loss of methylation testing' for Beckwith-Wiedemann syndrome (BWS) increases the diagnostic yield.
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Addition of H19 'loss of methylation testing' for Beckwith-Wiedemann syndrome (BWS) increases the diagnostic yield.

机译：Beckwith-Wiedemann综合征（BWS）的H19'甲基化损失检测'增加了诊断率。

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摘要

Beckwith-Wiedemann syndrome (BWS) is a clinical diagnosis; however, molecular confirmation via abnormal methylation of DMR2(LIT1) and/or DMR1(H19) has clinical utility due to epigenotype-tumor association. Despite the strong link between H19 hypermethylation and tumor risk, several diagnostic laboratories only test for hypomethylation of LIT1. We assessed the added diagnostic value of combined LIT1 and H19 testing in a large series of referred samples from 1298 patients, including 53 well-characterized patients from the St. Louis Children's Hospital BWS-Registry (validation samples) and 1245 consecutive nationwide referrals (practice samples). Methylation-sensitive enzymatic digestion with Southern hybridization assessed loss of normal imprinting. In the validation group, abnormal LIT1 hypomethylation was detected in 60% (32/52) of patients but LIT1/H19-combined testing was abnormal in 68% (36/53); sensitivity in the practice setting demonstrated 27% (342/1245) abnormal LIT1 and 32% (404/1245) abnormal LIT1/H19-combined. In addition, H19 methylation was abnormal in 7% of LIT1-normal patients. We observed absence of uniparental disomy (UPD) in 27% of combined LIT1/H19-abnormal samples, diagnostic of multilocus methylation abnormalities; in contrast to studies implicating that combined LIT1/H19 abnormalities are diagnostic of UPD. The overall low detection rate, even in validated patient samples and despite characterization of both loci and UPD status, emphasizes the importance of clinical diagnosis in BWS.
机译：Beckwith-Wiedemann综合征（BWS）是一种临床诊断;然而，由于表型与肿瘤的关系，通过DMR2（LIT1）和/或DMR1（H19）的异常甲基化进行分子确认具有临床意义。尽管H19甲基化水平高与肿瘤风险之间存在密切联系，但一些诊断实验室仅测试LIT1的甲基化程度低。我们评估了LIT1和H19联合检测在1298例患者的大量参考样本中的附加诊断价值，其中包括来自圣路易斯儿童医院BWS注册中心的53例特征明确的患者（验证样本）和1245例全国范围内的连续转诊（实践）样本）。 Southern杂交对甲基化敏感的酶消化评估了正常印迹的损失。在验证组中，在60％（32/52）的患者中检测到LIT1甲基化异常，但在68％（36/53）的患者中LIT1 / H19联合检测异常。在实践中的敏感性显示27％（342/1245）LIT1异常和32％（404/1245）LIT1 / H19异常组合。此外，LIT1正常患者中有7％的患者H19甲基化异常。我们观察到27％的LIT1 / H19组合异常样本中没有单亲二体性（UPD），可诊断多位点甲基化异常。与暗示LIT1 / H19合并异常可诊断UPD的研究相反。总体低检出率，即使在经过验证的患者样本中，尽管具有基因座和UPD状态的特征，也强调了BWS临床诊断的重要性。

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