Aissvarya Shankar, Ling King-Hwa, Arumugam Manohar, Thilakavathy Karuppiah
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Genetics & Regenerative Medicine Research Group, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
EFORT Open Rev. 2024 Aug 1;9(8):723-732. doi: 10.1530/EOR-23-0056.
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.
杜普伊特伦挛缩症(DC)是一种掌腱膜的纤维增生性疾病,其特征为手指屈曲挛缩,并与III型胶原蛋白的异常积聚有关。据报道,该疾病在北欧后裔中患病率最高。然而,这种疾病在全球范围内都有分布,患病率各不相同。DC是一种多因素疾病,遗传和环境因素都对该疾病的病因有影响。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,但关于外显子区域中发现的变异的报道却很少。大多数报道都比较陈旧,因此有必要重新评估这些变异,以进一步了解DC的遗传病因。在这篇综述中,我们首先强调DC的遗传方面和以前的遗传研究。随后,本文将讨论与DC相关的分子途径,并总结DC中外显子区域发现的遗传变异及其与分子途径的联系。总共报道了来自六个基因的九个变异,这些基因包含三个途径。报道的大多数变异都参与了Wnt信号通路。此外,所有鉴定出的变异都来自欧洲/白种人受试者,在外显子区域发现的变异都是错义变异。可以将这些发现与其他地区人群的变异进行比较,以确定出现频率最高的变异,作为DC的生物标志物或治疗靶点。