Park Hyung Jun, Lee Wookjae, Kim Se Hoon, Lee Jung Hwan, Shin Ha Young, Kim Seung Min, Park Kee Duk, Lee Ji Hyun, Choi Young Chul
Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.
Department of Chemistry, Yonsei University, Seoul, Korea.
Yonsei Med J. 2018 Mar;59(2):337-340. doi: 10.3349/ymj.2018.59.2.337.
Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array. Recent studies revealed that the FAT1 expression is associated with disease activity of FSHD, and the FAT1 alterations result in myopathy with a FSHD-like phenotype. We describe a 59-year-old woman with both contracted D4Z4 repeat units and a FAT1 mutation. Shoulder girdle muscle weakness developed at the age of 56 years, and was followed by proximal leg weakness. When we examined her at 59 years of age, she displayed asymmetric and predominant weakness of facial and proximal muscles. Muscle biopsy showed increased variation in fiber size and multifocal degenerating fibers with lymphocytic infiltration. Southern blot analysis revealed 8 D4Z4 repeat units, and targeted sequencing of modifier genes demonstrated the c.10331 A>G variant in the FAT1 gene. This FAT1 variant has previously been reported as pathogenic variant in a patient with FSHD-like phenotype. Our study is the first report of a FAT1 mutation in a FSHD1 patient, and suggests that FAT1 alterations might work as a genetic modifier.
1型面肩肱型肌营养不良症（FSHD1）由D4Z4重复序列阵列的收缩引起。最近的研究表明，FAT1表达与FSHD的疾病活动相关，且FAT1改变会导致具有FSHD样表型的肌病。我们描述了一名59岁女性，她既有收缩的D4Z4重复单元，又有FAT1突变。肩胛带肌无力在56岁时出现，随后出现近端腿部无力。当我们在她59岁时对其进行检查时，她表现出面部和近端肌肉不对称且以肌无力为主。肌肉活检显示纤维大小变异增加以及多灶性变性纤维伴淋巴细胞浸润。Southern印迹分析显示有8个D4Z4重复单元，修饰基因的靶向测序证实FAT1基因存在c.10331 A>G变异。该FAT1变异先前在一名具有FSHD样表型的患者中被报道为致病变异。我们的研究是FSHD1患者中FAT1突变的首例报告，并提示FAT1改变可能作为一种遗传修饰因子起作用。
