Alkorta-Aranburu Gorka, Sukhanova Madina, Carmody David, Hoffman Trevor, Wysinger Latrice, Keller-Ramey Jennifer, Li Zejuan, Johnson Amy Knight, Kobiernicki Frances, Botes Shaun, Fitzpatrick Carrie, Das Soma, Del Gaudio Daniela
J Pediatr Endocrinol Metab. 2016 May 1;29(5):523-31. doi: 10.1515/jpem-2015-0341.
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).
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.
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 ~64% of patients with NDM of unknown etiology.
MS-MLPA is a reliable method to identify all known 6q24 abnormalities and comprehensive testing of all causes reveals a causal mutation in ~64% of patients.
我们评估了一种甲基化特异性多重连接依赖探针扩增（MS-MLPA）检测方法，用于分子诊断由6q24异常引起的短暂性新生儿糖尿病（TNDM），并评估了将该检测方法与下一代测序（NGS）分析相结合用于诊断新生儿糖尿病（NDM）患者的临床实用性。
我们对18份对照样本和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检测。接下来，我们通过对11个NDM基因进行NGS分析并结合MS-MLPA检测，对22例前瞻性患者进行了评估。
在所有对照样本以及19%的6号染色体双亲遗传正常的患者中均鉴定出6q24畸变。MS-MLPA/NGS联合方法在约64%病因不明的NDM患者中确定了遗传病因。
MS-MLPA是一种可靠的方法，可识别所有已知的6q24异常，对所有病因进行全面检测可在约64%的患者中发现致病突变。
