PDF(Pubmed)
Abstract：
Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. To accommodate the challenge, we compiled a list of known progeroid syndromes and calculated the mean prevalence of their associated phenotypes, defining what we term the \'progeria phenome\'. The data were used to train a support vector machine that is available at https://www.mitodb.com and able to classify progerias based on phenotypes. Furthermore, this allowed us to investigate the correlation of progeroid syndromes and syndromes with various pathogenesis using hierarchical clustering algorithms and disease networks. We detected that ataxia-telangiectasia like disorder 2, spastic paraplegia 49 and Meier-Gorlin syndrome display strong association to progeroid syndromes, thereby implying that the syndromes are previously unrecognized progerias. In conclusion, our study has provided tools to evaluate the likelihood of a syndrome or patient being progeroid. This is a considerable step forward in our understanding of what constitutes a premature aging disorder and how to diagnose them.
摘要：
前驱体疾病是一组罕见且复杂的遗传性综合征，具有与正常衰老相关的多效性表型。由于临床表现的巨大差异，这些疾病给临床医生带来了诊断挑战，因此限制了医学研究。为了适应挑战，我们编制了一份已知的早衰综合征列表，并计算了其相关表型的平均患病率，定义我们所说的“早衰现象组”。数据用于训练支持向量机，可在https://www上获得。mitodb.com，并能够根据表型对预后进行分类。此外，这使我们能够使用分层聚类算法和疾病网络研究早衰综合征和综合征与各种发病机制的相关性.我们检测到共济失调-毛细血管扩张样障碍2，痉挛性截瘫49和Meier-Gorlin综合征与孕激素综合征有很强的相关性，从而暗示这些综合征是以前未被识别的疾病。总之,我们的研究提供了工具来评估综合征或患者为孕激素的可能性.这是我们对什么构成过早衰老障碍以及如何诊断它们的理解迈出的一大步。
