The Folkhälsan Institute of Genetics and the Department of Medical Genetics, University of Helsinki, Haartman Institute, Helsinki, Finland.
Neuromuscul Disord. 2013 Jan;23(1):56-65. doi: 10.1016/j.nmd.2012.07.007. Epub 2012 Sep 23.
Nemaline myopathy (NM) constitutes a heterogeneous group of congenital myopathies. Mutations in the nebulin gene (NEB) are the main cause of recessively inherited NM. NEB is one of the most largest genes in human. To date, 68 NEB mutations, mainly small deletions or point mutations have been published. The only large mutation characterized is the 2.5 kb deletion of exon 55 in the Ashkenazi Jewish population. To investigate any copy number variations in this enormous gene, we designed a novel custom comparative genomic hybridization microarray, NM-CGH, targeted towards the seven known genes causative for NM. During the validation of the NM-CGH array we identified two novel deletions in two different families. The first is the largest deletion characterized in NEB to date, (∼53 kb) encompassing 24 exons. The second deletion (1 kb) covers two exons. In both families, the copy number change was the second mutation to be characterized and shown to have been inherited from one of the healthy carrier parents. In addition to these novel mutations, copy number variation was identified in four samples in three families in the triplicate region of NEB. We conclude that this method appears promising for the detection of copy number variations in NEB.
先天性肌营养不良症（NM）是一组异质性先天性肌病。隐性遗传 NM 的主要原因是nebulin 基因（NEB）的突变。NEB 是人类最大的基因之一。迄今为止，已发表了 68 种 NEB 突变，主要是小型缺失或点突变。唯一特征化的大型突变是在阿什肯纳兹犹太人中发现的 55 号外显子 2.5 kb 的缺失。为了研究这个巨大基因中的任何拷贝数变异，我们设计了一种新型的定制比较基因组杂交微阵列 NM-CGH，针对已知的导致 NM 的七个基因。在 NM-CGH 阵列的验证过程中，我们在两个不同的家庭中发现了两个新的缺失。第一个是迄今为止在 NEB 中特征化的最大缺失，（∼53 kb）包含 24 个外显子。第二个缺失（1 kb）覆盖两个外显子。在两个家庭中，拷贝数变化是第二个被特征化的突变，并被证明是从一个健康的携带者父母遗传而来的。除了这些新的突变，在三个家庭的三个样本中，在 NEB 的三重复区域发现了拷贝数变异。我们的结论是，这种方法似乎很有希望用于检测 NEB 的拷贝数变异。
