Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
World J Pediatr. 2014 May;10(2):126-32. doi: 10.1007/s12519-014-0481-1. Epub 2014 May 7.
We determined the clinical and molecular genetic characteristics of 8 Chinese patients with Ullrich congenital muscular dystrophy (UCMD).
Clinical data of probands were collected and muscle biopsies of patients were analyzed. Exons of COL6A1, COL6A2 and COL6A3 were analyzed by direct sequencing. Mutations in COL6A1, COL6A2 and COL6A3 were identified in 8 patients.
Among these mutations, 5 were novel [three in the triple helical domain (THD) and 2 in the second C-terminal (C2) domain]. We also identified five known missense or in-frame deletion mutations in THD and C domains. Immunohistochemical studies on muscle biopsies from patients showed reduced level of collagen VI at the muscle basement membrane and mis-localization of the protein in interstitial and perivascular regions.
The novel mutations we identified underscore the importance of THD and C2 domains in the assembly and function of collagen VI, thereby providing useful information for the genetic counseling of UCMD patients.
我们确定了 8 名中国先天性肌营养不良症（UCMD）患者的临床和分子遗传特征。
收集先证者的临床资料，并对患者的肌肉活检进行分析。通过直接测序分析 COL6A1、COL6A2 和 COL6A3 的外显子。在 8 名患者中鉴定出 COL6A1、COL6A2 和 COL6A3 的突变。
这些突变中有 5 个是新的[三个在三螺旋域（THD），两个在第二个 C 末端（C2）域]。我们还在 THD 和 C 域中鉴定出五个已知的错义或框内缺失突变。对患者肌肉活检的免疫组织化学研究表明，胶原蛋白 VI 在肌肉基底膜的水平降低，并且蛋白在间质和血管周围区域发生错误定位。
我们鉴定的新突变强调了 THD 和 C2 域在胶原蛋白 VI 组装和功能中的重要性，从而为 UCMD 患者的遗传咨询提供了有用的信息。
