Pierson Christopher R, Agrawal Pankaj B, Blasko Jessica, Beggs Alan H
Department of Pathology, Division of Neuropathology, Children's Hospital Boston and Brigham, 300 Longwood Avenue, Boston, MA 02115, USA.
Neuromuscul Disord. 2007 Jul;17(7):562-8. doi: 10.1016/j.nmd.2007.03.010. Epub 2007 May 29.
We aimed to correlate pathologic findings with MTM1 mutation type in a series of molecularly defined XLMTM cases. Clinical data from 15 XLMTM patients and their corresponding 16 muscle biopsies were studied. All patients were infants (range: 6-217 days old) when initially biopsied. The proportion of myofibers with central nuclei did not correlate with clinical outcome, however, morphometric studies showed that survivors had larger myofiber diameters in infancy than those who died (10.4+/-3.9microm versus 8.9+/-3microm; p<0.001). As a corollary, patients with MTM1 missense mutations had larger myofiber diameters (11.1+/-4microm), than those with truncation/deletion mutations (8.6+/-2.7microm) (controls 11.7+/-2.5microm) (p<0.0001). These data indicate that differences in myofiber size correlate with MTM1 mutation type and patient outcome. Failure to attain and/or maintain myofiber size, along with fiber type perturbations and the misplacement of myofiber nuclei and other organelles, are important components of XLMTM muscle pathology.
我们旨在将一系列分子定义的X连锁型肌管性肌病（XLMTM）病例的病理结果与MTM1突变类型相关联。研究了15例XLMTM患者的临床数据及其相应的16份肌肉活检样本。所有患者初次活检时均为婴儿（年龄范围：6 - 217天）。有中央核的肌纤维比例与临床结局无关，然而，形态学研究表明，存活者婴儿期的肌纤维直径大于死亡者（10.4±3.9微米对8.9±3微米；p<0.001）。相应地，MTM1错义突变患者的肌纤维直径（11.1±4微米）大于截短/缺失突变患者（8.6±2.7微米）（对照组11.7±2.5微米）（p<0.0001）。这些数据表明，肌纤维大小的差异与MTM1突变类型和患者结局相关。未能达到和/或维持肌纤维大小，以及纤维类型紊乱、肌纤维核和其他细胞器的错位，是XLMTM肌肉病理学的重要组成部分。
