ColVI myopathies: where do we stand, where do we go?
ColVI myopathies: where do we stand, where do we go?
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DOI：
10.1186/2044-5040-1-30
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发表时间：
2011-09-23
期刊：
影响因子：
4.9
通讯作者：
Bonne G
中科院分区：
文献类型：
--
作者：
Allamand V;Briñas L;Richard P;Stojkovic T;Quijano-Roy S;Bonne G
VI 型胶原蛋白肌病是由编码 VI 型胶原蛋白 (ColVI) 的基因突变引起的，代表了乌尔里希先天性肌营养不良症 (UCMD) 和贝特莱姆肌病 (BM) 两端的临床连续体，以及介于两者之间的不太明确的中间表型。 ColVI 肌病还与其他与明显肌肉挛缩相关的疾病具有共同特征，这使得鉴别诊断变得困难。这组疾病长期以来未被充分认识，但在过去十年中引起了人们的极大兴趣，在理解其分子发病机制方面取得了重要进展。事实上，现在已经报道了 COL6A1、COL6A2 和 COL6A3 基因的大量突变，其中很大一部分是从头突变并产生显性失活效应。基因型-表型相关性也开始出现，反映了这些疾病中发挥作用的各种致病机制：显性的从头外显子剪接能够合成和分泌突变四聚体，而纯合无义突变则导致翻译过早终止和功能完全丧失，与早发的严重表型相关。在这篇综述中，我们介绍了 ColVI 肌病领域的诊断和研究现状。过去十年取得了重大进展，在 ColVI 肌病动物模型和患者样本中发现了细胞功能的改变。特别是，最近报道了线粒体功能障碍和骨骼肌自噬清除系统的缺陷，从而开辟了潜在的治疗途径。
Collagen VI myopathies, caused by mutations in the genes encoding collagen type VI (ColVI), represent a clinical continuum with Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) at each end of the spectrum, and less well-defined intermediate phenotypes in between. ColVI myopathies also share common features with other disorders associated with prominent muscle contractures, making differential diagnosis difficult. This group of disorders, under-recognized for a long time, has aroused much interest over the past decade, with important advances made in understanding its molecular pathogenesis. Indeed, numerous mutations have now been reported in the COL6A1, COL6A2 and COL6A3 genes, a large proportion of which are de novo and exert dominant-negative effects. Genotype-phenotype correlations have also started to emerge, which reflect the various pathogenic mechanisms at play in these disorders: dominant de novo exon splicing that enables the synthesis and secretion of mutant tetramers and homozygous nonsense mutations that lead to premature termination of translation and complete loss of function are associated with early-onset, severe phenotypes. In this review, we present the current state of diagnosis and research in the field of ColVI myopathies. The past decade has provided significant advances, with the identification of altered cellular functions in animal models of ColVI myopathies and in patient samples. In particular, mitochondrial dysfunction and a defect in the autophagic clearance system of skeletal muscle have recently been reported, thereby opening potential therapeutic avenues.
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不同的区域控制转基因小鼠不同组织中α1（VI）胶原蛋白启动子的转录激活。
DOI：
10.1083/jcb.135.4.1163
发表时间：
1996-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Braghetta P;Fabbro C;Piccolo S;Marvulli D;Bonaldo P;Volpin D;Bressan GM
通讯作者：
Bressan GM
影响因子：
3.3
作者：
Blaauw, Bert;Agatea, Lisa;Reggiani, Carlo
通讯作者：
Reggiani, Carlo
DOI：
10.1111/j.1749-6632.1985.tb51154.x
发表时间：
1985-12-30
影响因子：
5.2
作者：
ENGEL, J;FURTHMAYR, H;TIMPL, R
通讯作者：
TIMPL, R
影响因子：
3.5
作者：
Bonaldo, P;Braghetta, P;Bressan, GM
通讯作者：
Bressan, GM
DOI：
10.1073/pnas.0610270104
发表时间：
2007-01-16
影响因子：
11.1
作者：
Angelin, Alessia;Tiepolo, Tania;Bernardi, Paolo
通讯作者：
Bernardi, Paolo