The utility of exome sequencing in diagnosing pediatric neurodevelopmental disorders in a highly consanguineous
Tamam Khalaf1, Mode Al Ojaimi2,3, Dina Amin Saleh4,5
1Genetic Counseling Division, Igenomix, Dubai, UAE.
Insights
Exome sequencing effectively diagnosed neurodevelopmental disorders in a consanguineous population. The study identified novel genetic variants and candidate genes, improving diagnostic yield in this unique cohort.
Area of Science:
- Genetics
- Pediatrics
- Medical Diagnostics
Background:
- Neurodevelopmental manifestations in children often present diagnostic challenges.
- Exome sequencing (ES) is a powerful tool for genetic diagnosis.
- Consanguineous populations may have a higher prevalence of recessive genetic disorders.
Purpose of the Study:
- To evaluate the diagnostic utility of exome sequencing (ES) in children with neurodevelopmental complaints within a highly consanguineous population.
- To identify genetic variants, including novel ones and candidate genes, associated with these disorders.
- To assess the impact of ES on clinical management and treatment plans.
Main Methods:
- Retrospective chart review of 405 children with neurodevelopmental complaints undergoing ES.
- Evaluation across multiple centers in the United Arab Emirates over a four-year period.
- Analysis of consanguinity rates, clinical presentations, diagnostic yield, and variant types.
Main Results:
- A diagnostic yield of 57% was achieved in the cohort.
- Novel variants were identified in 54% of positive cases.
- Copy number variants (CNVs) and candidate genes were identified; treatment plans were altered in 6% of positive cases.
Conclusions:
- Exome sequencing demonstrates high diagnostic utility in consanguineous populations with neurodevelopmental disorders.
- ES facilitates the identification of novel genetic variants, candidate genes, and secondary findings.
- The diagnostic information obtained from ES can lead to altered treatment plans and improved patient management.
Abstract:
Exome sequencing (ES) has been utilized in diagnosing children with neurodevelopmental manifestations, this study aimed to investigate the utility of ES in children within a highly consanguineous population that presented with neurodevelopmental complaints. A retrospective chart review was performed for 405 children with neurodevelopmental complaints who have had ES and were evaluated in multiple centers in the United Arab Emirates over a four-year period. Within the cohort of 405 children, consanguinity was reported in 35% (144/405). The primary clinical presentations were developmental delay/cognitive impairment, distinctive facial features, hypotonia, seizures, and weakness. The diagnostic yield was 57% (231/405). Novel variants were identified in 54% (125/231) of positive cases. Within the positive cases, specific treatment was available in 6% (13/231) and copy number variants (CNV) were reported in 3% (8/231) of cases. In eight children, variants in genes that have not yet been linked to human disease that could potentially be the cause of the observed phenotype "candidate genes" were identified. ES was utilized effectively within this cohort with a high diagnostic yield and through the identification of novel gene variants, CNVs, candidate genes and secondary findings as well as the alteration of the treatment plan in cases where treatment was available.
