Abstract
BackgroundSpastic cerebral palsy (CP) is a leading cause of physical disability. Most people with spastic CP are born with it, but early diagnosis is challenging, and no current biomarker platform readily identifies affected individuals. The aim of this study was to evaluate epigenetic profiles as biomarkers for spastic CP. A novel analysis pipeline was employed to assess DNA methylation patterns between peripheral blood cells of adolescent subjects (14.9 ± 0.3 years old) with spastic CP and controls at single CpG site resolution.ResultsSignificantly hypo- and hyper-methylated CpG sites associated with spastic CP were identified. Nonmetric multidimensional scaling fully discriminated the CP group from the controls. Machine learning based classification modeling indicated a high potential for a diagnostic model, and 252 sets of 40 or fewer CpG sites achieved near-perfect accuracy within our adolescent cohorts. A pilot test on significantly younger subjects (4.0 ± 1.5 years old) identified subjects with 73% accuracy.ConclusionsAdolescent patients with spastic CP can be distinguished from a non-CP cohort based on DNA methylation patterns in peripheral blood cells. A clinical diagnostic test utilizing a panel of CpG sites may be possible using a simulated classification model. A pilot validation test on patients that were more than 10 years younger than the main adolescent cohorts indicated that distinguishing methylation patterns are present earlier in life. This study is the first to report an epigenetic assay capable of distinguishing a CP cohort.
Highlights
Spastic cerebral palsy (CP) is a leading cause of physical disability
Methylation patterns were analyzed in 32 genomic DNA samples from peripheral blood cells: 16 subjects with a diagnosis of spastic CP (13 males, 3 females; age = 14.7 ± 3.3) and 16 controls (15 males, 1 female; age = 15.0 ± 2.2)
DNA methylation assays have not been broadly applied in the study of CP biomarkers; recent studies suggest that differences in the prevalence of CP in monozygotic twins may be associated with alterations in DNA methylation [37, 38], and numerous studies have demonstrated that various stress stimuli, such as hypoxia, infection, and inflammation, cause a long-lasting change to DNA methylation patterns [22]
Summary
Spastic cerebral palsy (CP) is a leading cause of physical disability. Most people with spastic CP are born with it, but early diagnosis is challenging, and no current biomarker platform readily identifies affected individuals. Medicaid data show that annual medical costs are 10–26 times higher for children with CP [6], and problems continue into adulthood with poor access to care, lower employment, absenteeism, disability, and CP arises from a disturbance in the brain, which in most cases occurs prenatally between 24 weeks gestation and birth [2, 8]. Studies indicate that 20–33% of infants who developed CP lacked detectable brain abnormalities on cranial ultrasound evaluation, and MRI and CT imaging data suggest that at least 17% of known CP patients have no detectable brain malformation [9, 10]. Many children exhibit brain imaging indicative of CP even though they do not develop CP [11], and imaging approaches have shown promise as prognostic
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
