Vanakker Olivier, Callewaert Bert, Malfait Fransiska, Coucke Paul
Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium; email:
Annu Rev Genomics Hum Genet. 2015;16:229-55. doi: 10.1146/annurev-genom-090314-050039. Epub 2015 May 18.
Over the last few years, the field of hereditary connective tissue disorders has changed tremendously. This review highlights exciting insights into three prototypic disorders affecting the soft connective tissue: Ehlers-Danlos syndrome, pseudoxanthoma elasticum, and cutis laxa. For each of these disorders, the identification and characterization of several novel but related conditions or subtypes have widened the phenotypic spectrum. In parallel, the vast underlying molecular network connecting these phenotypes is progressively being uncovered. Identification and characterization (both clinical and molecular) of new phenotypes within the connective tissue disorder spectrum are often key to further unraveling the pathways involved in connective tissue biology and delineating the clinical spectrum and pathophysiology of the disorders. Although difficult challenges remain, recent findings have expanded our pathophysiological understanding and may lead to targeted therapies in the near future.
在过去几年中,遗传性结缔组织疾病领域发生了巨大变化。本综述重点介绍了对三种影响软结缔组织的典型疾病的令人兴奋的见解:埃勒斯-当洛综合征、弹性假黄瘤和皮肤松弛症。对于这些疾病中的每一种,几种新的但相关的病症或亚型的鉴定和表征拓宽了表型谱。与此同时,连接这些表型的庞大潜在分子网络正逐渐被揭示。在结缔组织疾病谱内鉴定和表征(临床和分子方面)新表型通常是进一步阐明结缔组织生物学所涉及的途径以及描绘这些疾病的临床谱和病理生理学的关键。尽管仍然存在艰巨挑战,但最近的发现扩展了我们对病理生理学的理解,并可能在不久的将来带来靶向治疗。