Voermans N C, Bönnemann C G, Huijing P A, Hamel B C, van Kuppevelt T H, de Haan A, Schalkwijk J, van Engelen B G, Jenniskens G J
Neuromuscular Centre Nijmegen, Department of Neurology, 935, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Neuromuscul Disord. 2008 Nov;18(11):843-56. doi: 10.1016/j.nmd.2008.05.017. Epub 2008 Sep 24.
This review presents an overview of myopathies and inherited connective tissue disorders that are caused by defects in or deficiencies of molecules within the extracellular matrix (ECM). We will cover the myopathies caused by defects in transmembrane protein complexes (dystroglycan, sarcoglycan, and integrins), laminin, and collagens (collagens VI, XIII, and XV). Clinical characteristics of several of these myopathies imply skin and joint features. We subsequently describe the inherited connective tissue disorders that are characterized by mild to moderate muscle involvement in addition to the dermal, vascular, or articular symptoms. These disorders are caused by defects of matrix-embedded ECM molecules that are also present within muscle (collagens I, III, V, IX, lysylhydroxylase, tenascin, fibrillin, fibulin, elastin, and perlecan). By focussing on the structure and function of these ECM molecules, we aim to point out the clinical and molecular overlap between the groups of disorders. We argue that clinicians and researchers dealing with myopathies and inherited connective tissue disorders should be aware of this overlap. Only a multi-disciplinary approach will allow full recognition of the wide variety of symptoms present in the spectrum of ECM defects, which has important implications for scientific research, diagnosis, and for the treatment of these disorders.
本综述概述了由细胞外基质（ECM）中分子缺陷或缺乏引起的肌病和遗传性结缔组织疾病。我们将涵盖由跨膜蛋白复合物（肌营养不良聚糖、肌聚糖和整合素）、层粘连蛋白和胶原蛋白（VI型、XIII型和XV型胶原蛋白）缺陷引起的肌病。其中几种肌病的临床特征提示有皮肤和关节方面的表现。随后，我们将描述遗传性结缔组织疾病，这些疾病除了有皮肤、血管或关节症状外，还伴有轻度至中度的肌肉受累。这些疾病是由肌肉中也存在的基质嵌入ECM分子缺陷引起的（I型、III型、V型、IX型胶原蛋白、赖氨酰羟化酶、腱生蛋白、原纤蛋白、纤连蛋白、弹性蛋白和基底膜聚糖）。通过关注这些ECM分子的结构和功能，我们旨在指出这些疾病组之间的临床和分子重叠之处。我们认为，处理肌病和遗传性结缔组织疾病的临床医生和研究人员应该意识到这种重叠。只有采用多学科方法，才能全面认识ECM缺陷谱系中存在的各种症状，这对这些疾病的科学研究、诊断和治疗具有重要意义。
