Folkhälsan Research Center, Helsinki, Finland; Department of Medical Genetics, Medicum, University of Helsinki, Finland.
Folkhälsan Research Center, Helsinki, Finland; Department of Medical Genetics, Medicum, University of Helsinki, Finland.
Neuromuscul Disord. 2021 Jun;31(6):539-545. doi: 10.1016/j.nmd.2021.03.006. Epub 2021 Mar 23.
We report the first mosaic mutation, a deletion of exons 11-107, identified in the nebulin gene in a Finnish patient presenting with a predominantly distal congenital myopathy and asymmetric muscle weakness. The female patient is ambulant and currently 26 years old. Muscle biopsies showed myopathic features with type 1 fibre predominance, strikingly hypotrophic type 2 fibres and central nuclei, but no nemaline bodies. The deletion was detected in a copy number variation analysis based on next-generation sequencing data. The parents of the patient did not carry the deletion. Mosaicism was detected using a custom, targeted comparative genomic hybridisation array. Expression of the truncated allele, less than half the size of full-length nebulin, was confirmed by Western blotting. The clinical and histological picture resembled that of a family with a slightly smaller deletion, and that in patients with recessively inherited distal forms of nebulin-caused myopathy. Asymmetry, however, was a novel feature.
我们报告了首例镶嵌突变，即一个在 nebulin 基因中外显子 11-107 的缺失，该突变存在于一位芬兰患者中，其表现为主要为远端先天性肌病和非对称性肌无力。这位女性患者可自主行走，目前 26 岁。肌肉活检显示具有肌病特征，Ⅰ型纤维占优势，明显的小纤维型 2 纤维和中央核，但无杆状体。缺失是在基于下一代测序数据的拷贝数变异分析中发现的。患者的父母未携带缺失。使用定制的靶向比较基因组杂交阵列检测到镶嵌现象。通过 Western blot 证实截断等位基因的表达，其大小不到全长 nebulin 的一半。临床和组织学表现类似于携带略小缺失的家族，以及隐性遗传的 nebulin 引起的远端肌病的患者。然而，非对称性是一个新的特征。
