PDF(Pubmed)
Abstract：
Dupuytren\'s contracture (DC) is a fibroproliferative disorder of the palmar fascia characterised by the digits\' flexion contractures and is associated with abnormal build-up of type III collagen. The prevalence of the disease is reported to be highest among Northern European descendants. However, the disease is widespread globally with varying prevalence. DC is a multifactorial disease, having both genetic and environmental factors contributing to the causality of the disease. Over the years, various studies have been conducted to understand the molecular mechanism and genetic aspects of DC but there is a lack of reports on the variants found in the exonic regions. Most reports are backdated making it necessary to re-evaluate the variants to further understand the genetic aetiology of DC. In this review, we first highlight the genetic aspects and previous genetic studies on DC. The report is followed by a discussion on the molecular pathways suggested to be associated with DC and a summary of the genetic variants in the exonic regions found in DC and their connections with the molecular pathways. A total of nine variants were reported originating from six genes comprising three pathways. Most variants reported are involved in the Wnt signalling pathway. Moreover, all variants identified are in European/Caucasian subjects and the variants found in the exonic regions are missense variants. A comparison of these findings with variants from populations of other regions can be conducted to identify the variants with the most occurrence to act as biomarkers or therapeutic targets for DC.
摘要：
Dupuytren挛缩症（DC）是掌肌筋膜的一种纤维增生性疾病，以手指屈曲挛缩为特征，并与III型胶原蛋白的异常积累有关。据报道，该疾病的患病率在北欧后裔中最高。然而,该疾病在全球范围内普遍存在，患病率各不相同。DC是一种多因素疾病,具有遗传和环境因素导致疾病的因果关系。多年来,已经进行了各种研究来了解DC的分子机制和遗传方面，但缺乏关于外显子区域中发现的变异的报道。大多数报告都已过时，因此有必要重新评估变体以进一步了解DC的遗传病因。在这次审查中,我们首先强调DC的遗传方面和以前的遗传研究。报告之后是对建议与DC相关的分子途径的讨论，以及在DC中发现的外显子区域中的遗传变异及其与分子途径的联系的总结。报道了总共9种变体源自包含三种途径的6种基因。报道的大多数变体涉及Wnt信号传导途径。此外，鉴定出的所有变异体均存在于欧洲/高加索受试者中,在外显子区域发现的变异体是错义变异体.可以进行这些发现与来自其他区域的群体的变体的比较,以鉴定具有最多发生率的变体作为DC的生物标志物或治疗靶标。
