De Franco E, Caswell R, Houghton J A L, Iotova V, Hattersley A T, Ellard S
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
University Hospital 'St. Marina', Varna, Bulgaria.
Diabet Med. 2017 Apr;34(4):582-585. doi: 10.1111/dme.13180. Epub 2016 Jul 31.
An early genetic diagnosis of neonatal diabetes guides clinical management and results in improved treatment in ~ 40% of patients. In the offspring of individuals with neonatal diabetes, a prenatal diagnosis allows accurate estimation of the risk of developing diabetes and, eventually, the most appropriate treatment for the baby. In this study, we performed non-invasive prenatal genetic testing for a fetus at risk of inheriting a paternal KCNJ11 p.R201C mutation causing permanent neonatal diabetes.
A droplet digital polymerase chain reaction assay was used to detect the presence of the mutation in cell-free circulating DNA (cfDNA) extracted from maternal plasma at 12 and 16 weeks' gestation.
The mutation was not detected in the cfDNA samples, suggesting that the fetus had not inherited the KCNJ11 mutation. The fetal DNA fraction was estimated at 6.2% and 10.7%, which is above the detection limit of the assay. The result was confirmed by Sanger sequencing after the baby's birth, confirming that the baby's risk of developing neonatal diabetes was reduced to that of the general population.
We report the first case of non-invasive prenatal testing in a family with neonatal diabetes. A prenatal diagnosis in families at high risk of monogenic diabetes informs both prenatal and postnatal management. Although the clinical impact of this novel technology still needs to be assessed, its implementation in clinical practice (including cases at risk of inheriting mutations from the mother) will likely have a positive impact upon the clinical management of families affected by monogenic diabetes.
新生儿糖尿病的早期基因诊断可指导临床管理，并使约40%的患者治疗得到改善。对于患有新生儿糖尿病个体的后代，产前诊断可准确估计患糖尿病的风险，并最终为婴儿提供最合适的治疗。在本研究中，我们对一名有遗传父源性KCNJ11 p.R201C突变导致永久性新生儿糖尿病风险的胎儿进行了无创产前基因检测。
采用液滴数字聚合酶链反应分析检测妊娠12周和16周时从母体血浆中提取的游离循环DNA（cfDNA）中是否存在该突变。
在cfDNA样本中未检测到该突变，表明胎儿未遗传KCNJ11突变。估计胎儿DNA比例为6.2%和10.7%，高于该检测方法的检测限。婴儿出生后通过桑格测序证实了该结果，确认婴儿患新生儿糖尿病的风险已降至一般人群水平。
我们报告了首例在患有新生儿糖尿病的家庭中进行无创产前检测的病例。对单基因糖尿病高危家庭进行产前诊断可为产前和产后管理提供依据。尽管这项新技术的临床影响仍需评估，但其在临床实践中的应用（包括有从母亲遗传突变风险的病例）可能会对受单基因糖尿病影响的家庭的临床管理产生积极影响。
