Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach
Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach
复制标题
DOI：
10.1515/jpem-2015-0341
复制
发表时间：
2016-05-01
影响因子：
1.4
通讯作者：
del Gaudio, Daniela
中科院分区：
文献类型：
--
作者：
Alkorta-Aranburu, Gorka;Sukhanova, Madina;del Gaudio, Daniela
背景资料：我们评估了甲基化特异性多重连接依赖性探针扩增（MS-MLPA）测定用于由6 q24异常引起的短暂性新生儿糖尿病（TNDM）的分子诊断，并评估了将该测定与下一代测序（NGS）分析结合用于诊断新生儿糖尿病（NDM）患者的临床效用。我们对18例对照样本和42例6号染色体双亲遗传正常的回顾性NDM病例进行了MS-MLPA。接下来，我们评估了22个前瞻性患者相结合的NGS分析11 NDM基因和MS-MLPA assay.Results：6 q24畸变被确定在所有控制和19%的患者与正常的双亲遗传的染色体6。MS-MLPA/NGS相结合的方法确定了类似于64%的患者与NDM的病因不明的遗传cause.Conclusions：MS-MLPA是一种可靠的方法，以确定所有已知的6 q24异常和全面测试的所有原因揭示了类似于64%的患者的因果突变。
Background: We evaluated a methylation-specific multiplex-ligation-dependent probe amplification (MS-MLPA) assay for the molecular diagnosis of transient neonatal diabetes mellitus (TNDM) caused by 6q24 abnormalities and assessed the clinical utility of using this assay in combination with next generation sequencing (NGS) analysis for diagnosing patients with neonatal diabetes (NDM).Methods: We performed MS-MLPA in 18 control samples and 42 retrospective NDM cases with normal bi-parental inheritance of chromosome 6. Next, we evaluated 22 prospective patients by combining NGS analysis of 11 NDM genes and the MS-MLPA assay.Results: 6q24 aberrations were identified in all controls and in 19% of patients with normal bi-parental inheritance of chromosome 6. The MS-MLPA/NGS combined approach identified a genetic cause in similar to 64% of patients with NDM of unknown etiology.Conclusions: MS-MLPA is a reliable method to identify all known 6q24 abnormalities and comprehensive testing of all causes reveals a causal mutation in similar to 64% of patients.