Unit of Bologna, CNR-Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza", 40136 Bologna, Italy.
IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Int J Environ Res Public Health. 2022 Jan 23;19(3):1252. doi: 10.3390/ijerph19031252.
Ullrich congenital muscular dystrophy (UCMD) is a severe form of muscular dystrophy caused by the loss of function of collagen VI, a critical component of the muscle-tendon matrix. Magnetic resonance imaging of UCMD patients' muscles shows a peculiar rim of abnormal signal at the periphery of each muscle, and a relative sparing of the internal part. The mechanism/s involved in the early fat substitution of muscle fiber at the periphery of muscles remain elusive. We studied a muscle biopsy of the rectus femoris/deep fascia (DF) of a 3-year-old UCMD patient, with a homozygous mutation in the gene. By immunohistochemical and ultrastructural analysis, we found a marked fatty infiltration at the interface of the muscle with the epimysium/DF and an atrophic phenotype, primarily in fast-twitch fibers, which has never been reported before. An unexpected finding was the widespread increase of interstitial cells with long cytoplasmic processes, consistent with the telocyte phenotype. Our study documents for the first time in a muscle biopsy the peculiar pattern of outside-in muscle degeneration followed by fat substitution as already shown by muscle imaging, and an increase of telocytes in the interstitium of the deep fascia, which highlights a potential involvement of this structure in the pathogenesis of UCMD.
乌利希先天性肌营养不良症（UCMD）是一种严重的肌肉营养不良症，由胶原蛋白 VI 功能丧失引起，胶原蛋白 VI 是肌肉-肌腱基质的关键组成部分。UCMD 患者肌肉的磁共振成像显示，每个肌肉的外周有一个异常信号的奇特边缘，内部部分相对保留。肌肉纤维外周早期脂肪替代的机制仍不清楚。我们研究了一名 3 岁 UCMD 患者的股直肌/深筋膜（DF）肌肉活检，该患者携带基因的纯合突变。通过免疫组织化学和超微结构分析，我们发现肌肉与外膜/DF 的界面处有明显的脂肪浸润和萎缩表型，主要是快肌纤维，这是以前从未报道过的。一个意外的发现是间质细胞的广泛增加，具有长细胞质突起，与间质细胞表型一致。我们的研究首次在肌肉活检中记录了从外向内的肌肉退化，随后是脂肪替代的特殊模式，正如肌肉成像所显示的那样，以及深筋膜间质中间质细胞的增加，这突出了这种结构在 UCMD 发病机制中的潜在作用。
