PDF(Pubmed)
Abstract：
NEB mutation is associated with congenital nemaline myopathies. Here, we report a family with recurrent prenatal arthrogryposis. Trio whole exome sequencing (WES) disclosed three novel NEB (NM_001271208.2) variants including one paternal frameshift c.19049_19050delCA (p.Thr6350Argfs*14) and two double maternal variants in cis c. [24871G>T;24871-10C>G] (p. [Val8291Phe;?]). They are evaluated as \"likely pathogenic (LP)\", \"variant of uncertain of significance (VUS)\", and \"VUS\", respectively. After further prediction, the c.24871G>T, c.24871-10C>G, and c.[24871G>T;24871-10C>G] were respectively genetically engineered into the three plasmids. Compared with their wild-type counterparts, the three plasmids all produced truncated transcripts, and also a significant proportion of the full-length transcripts, which allowed us to reclassify NEB c.24871G>T and c.24871-10C>G variants as LP. As far as we know, this is the first case carrying NEB allele-specific function of partial loss. This result helped the couple make informed reproductive choices and opt for assisted reproduction for future pregnancies. This study also increased awareness to the phenotype of prenatal nemaline myopathy and expanded the variant spectrum of NEB.
摘要：
NEB突变与先天性线虫性肌病有关。这里,我们报告了一个患有复发性产前关节炎的家庭。Trio全外显子组测序（WES）公开了三种新的NEB（NM_001271208.2）变体，包括一个父系移码c.19049_19050delCA（p。Thr6350Argfs*14）和顺式c中的两个双母体变体。[24871G>T；24871-10C>G]（p。[Val8291Phe；？]）。它们被评估为“可能致病(LP)”，“显著性不确定变体(VUS)”，和“VUS”，分别。经过进一步的预测,c.24871G>T，c.24871-10C>G，和c。[24871G>T;24871-10C>G]分别被基因工程改造到三个质粒中。与它们的野生型对应物相比，这三个质粒都产生了截短的转录本，还有相当比例的全长转录本，这使我们能够将NEBc.24871G>T和c.24871-10C>G变体重新分类为LP。据我们所知,这是首例携带NEB等位基因特异性功能部分缺失的病例。这一结果帮助这对夫妇做出明智的生殖选择，并为将来的怀孕选择辅助生殖。这项研究还提高了对产前线虫肌病表型的认识，并扩大了NEB的变异范围。
