Movaghar Arezoo, Page David, Scholze Danielle, Hong Jinkuk, DaWalt Leann Smith, Kuusisto Finn, Stewart Ron, Brilliant Murray, Mailick Marsha
Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Genet Med. 2021 Jul;23(7):1273-1280. doi: 10.1038/s41436-021-01144-7. Epub 2021 Mar 26.
Fragile X syndrome (FXS), the most prevalent inherited cause of intellectual disability, remains underdiagnosed in the general population. Clinical studies have shown that individuals with FXS have a complex health profile leading to unique clinical needs. However, the full impact of this X-linked disorder on the health of affected individuals is unclear and the prevalence of co-occurring conditions is unknown.
We mined the longitudinal electronic health records from more than one million individuals to investigate the health characteristics of patients who have been clinically diagnosed with FXS. Additionally, using machine-learning approaches, we created predictive models to identify individuals with FXS in the general population.
Our discovery-oriented approach identified the associations of FXS with a wide range of medical conditions including circulatory, endocrine, digestive, and genitourinary, in addition to mental and neurological disorders. We successfully created predictive models to identify cases five years prior to clinical diagnosis of FXS without relying on any genetic or familial data.
Although FXS is often thought of primarily as a neurological disorder, it is in fact a multisystem syndrome involving many co-occurring conditions, some primary and some secondary, and they are associated with a considerable burden on patients and their families.
脆性X综合征（FXS）是最常见的遗传性智力障碍病因，在普通人群中仍未得到充分诊断。临床研究表明，FXS患者具有复杂的健康状况，导致独特的临床需求。然而，这种X连锁疾病对受影响个体健康的全面影响尚不清楚，共病情况的患病率也未知。
我们挖掘了来自100多万人的纵向电子健康记录，以调查临床诊断为FXS的患者的健康特征。此外，我们使用机器学习方法创建了预测模型，以识别普通人群中的FXS患者。
我们基于发现的方法确定了FXS与广泛的医疗状况之间的关联，包括循环系统、内分泌、消化和泌尿生殖系统疾病，以及精神和神经疾病。我们成功创建了预测模型，能够在不依赖任何基因或家族数据的情况下，在临床诊断FXS的五年前识别出病例。
尽管FXS通常主要被认为是一种神经疾病，但实际上它是一种多系统综合征，涉及许多共病情况，有些是原发性的，有些是继发性的，它们给患者及其家庭带来了相当大的负担。
