Willis T A, Wood C L, Hudson J, Polvikoski T, Barresi R, Lochmüller H, Bushby K, Straub V
John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, UK.
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
Clin Genet. 2016 Aug;90(2):166-70. doi: 10.1111/cge.12695. Epub 2016 Jan 8.
Four and a half LIM protein 1 (FHL1/SLIM1) has recently been identified as the causative gene mutated in four distinct diseases affecting skeletal muscle that have overlapping features, including reducing body myopathy, X-linked myopathy, X-linked dominant scapuloperoneal myopathy and Emery-Dreifuss muscular dystrophy. FHL1 localises to the sarcomere and the sarcolemma and is believed to participate in muscle growth and differentiation as well as in sarcomere assembly. We describe in this case report a boy with a deletion of the entire FHL1 gene who is now 15 years of age and presented with muscle hypertrophy, reduced subcutaneous fat, rigid spine and short stature. This case is the first, to our knowledge, with a complete loss of the FHL1 protein and MAP7D3 in combination. It supports the theory that dominant negative effects (accumulation of cytotoxic-mutated FHL1 protein) worsen the pathogenesis. It extends the phenotype of FHL1-related myopathies and should prompt future testing in undiagnosed patients who present with unexplained muscle hypertrophy, contractures and rigid spine, particularly if male.
四半LIM结构域蛋白1（FHL1/SLIM1）最近被确定为四种影响骨骼肌的不同疾病中的致病基因，这些疾病具有重叠特征，包括肢带型肌病、X连锁肌病、X连锁显性肩胛腓骨肌病和Emery-Dreifuss肌营养不良症。FHL1定位于肌节和肌膜，被认为参与肌肉生长和分化以及肌节组装。在本病例报告中，我们描述了一名15岁男孩，其整个FHL1基因缺失，表现为肌肉肥大、皮下脂肪减少、脊柱僵硬和身材矮小。据我们所知，该病例是首例同时完全缺失FHL1蛋白和MAP7D3的病例。它支持这样一种理论，即显性负效应（细胞毒性突变FHL1蛋白的积累）会加重发病机制。它扩展了FHL1相关肌病的表型，应促使对出现不明原因肌肉肥大、挛缩和脊柱僵硬的未确诊患者，尤其是男性患者进行进一步检测。
