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Contribution of Congenital Heart Disorders Associated With Copy Number Variants in Mediating Risk for Brain Developmental Disorders: Evidence From 20-Year Retrospective Cohort Study
- Source :
- Frontiers in Cardiovascular Medicine, Vol 8 (2021), Frontiers in Cardiovascular Medicine
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Rare pathogenic copy number variants (CNVs) are genetic rearrangements that have been associated with an increased risk for congenital heart disorders (CHDs). However, the association of CNVs with atypical brain development, leading to neurodevelopmental disorders (NDDs), in the presence of CHDs remains unclear. We attempted to explore this association by establishing the prevalence and burden of CNVs associated with CHD in a Welsh population and by studying the effect of rare CNVs associated with CHDs in mediating the risk of NDDs. Toward this goal, we analyzed data from the Congenital Anomaly Register for Wales (CARIS), referred from hospitals in Wales between 1998 and 2018, which included 1,113 subjects in total. Of these, 785 subjects were included in the study following application of the exclusion criteria, and a total of 28 rare CNVs associated with CHD were analyzed. The findings from this cohort study identified 22q11.2 deletion as the most prominent CNV across the cohort. Our data demonstrates that the survival rate of the cohort after 3 years was 99.9%, and mortality fell significantly between 1 and 2 years and between 2 and 3 years [F(1,27) = 10, p = 0.0027; F(1,27) = 5.8, p = 0.0222]. Importantly, the data set revealed a positive correlation between the incidence of congenital heart disease and the incidence of neurodevelopmental abnormalities in patients with CNVs across the whole cohort [95% CI (0.4062, 0.8449), p < 0.0001, r = 0.6829]. Additionally, we identified significant CNVs that result in the co-morbidity of CHD and NDD and show that septal defects and global developmental delay are major congenital defects. Further research should identify a common molecular mechanism leading to the phenotypic comorbidity of CHDs and NDDs, arising from a common CNV, which can have an implication for improving risk classification and for fetal neuroprotection strategies in the affected children and in precision medicine.
- Subjects :
- 0301 basic medicine
Pediatrics
medicine.medical_specialty
congenital heart disorder
retrospective study
Cardiovascular Medicine
030204 cardiovascular system & hematology
03 medical and health sciences
Heart disorder
0302 clinical medicine
mental disorders
medicine
Diseases of the circulatory (Cardiovascular) system
Global developmental delay
Original Research
22q11 deletion syndrome
business.industry
neurodevelopmental disorders
Incidence (epidemiology)
Retrospective cohort study
medicine.disease
Comorbidity
030104 developmental biology
Congenital heart disorder
RC666-701
Cohort
Cardiology and Cardiovascular Medicine
business
copy number variants
Cohort study
Subjects
Details
- ISSN :
- 2297055X
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in Cardiovascular Medicine
- Accession number :
- edsair.doi.dedup.....838d4bebb920ee8f73d2c9874fb1cf4e