Monogenic defects in Russian children with autism spectrum disorders
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View abstract on PubMed
Summary
This summary is machine-generated.Rare genetic variants are a significant cause of autism spectrum disorder (ASD) in Russian children. Clinical exome sequencing effectively identified these variants, highlighting the genetic diversity underlying ASD.
Area Of Science
- Genetics
- Neurodevelopmental Disorders
- Pediatrics
Background
- Autism spectrum disorders (ASD) affect over 1% of children globally, often co-occurring with intellectual disability and speech delay.
- The high heterogeneity and phenotypical overlap of ASD present challenges in identifying specific genetic determinants.
- Understanding the genetic basis of ASD is crucial for diagnosis and potential therapeutic strategies.
Purpose Of The Study
- To investigate the spectrum and frequency of rare genetic variants in ASD-associated genes within a Russian pediatric cohort.
- To identify monogenic causes and variants of unknown significance contributing to ASD.
- To assess the utility of clinical exome sequencing in diagnosing genetic causes of ASD.
Main Methods
- Recruited 110 patients (106 families) with ASD, predominantly with co-occurring developmental delay or intellectual disability.
- Utilized chromosomal microarray analysis for patients with syndromic features.
- Performed clinical exome sequencing on remaining patients, focusing on rare variants (MAF ≤ 0.001) in high-confidence ASD-associated genes.
Main Results
- Pathogenic copy number variations were identified in 7% of patients.
- Clinical exome sequencing detected pathogenic/likely pathogenic variants in 11% of cases, revealing various monogenic syndromes.
- Rare variants of unknown significance were found in 26% of patients across numerous ASD-associated genes, including recurrent variants in *TRIP12*, *AUTS2*, *ARID1B*, *PCDH19*, and *EP300*.
- Confirmed that hemizygous males with *PCDH19* variants can exhibit neurobehavioral abnormalities.
Conclusions
- The genetic causes of ASD are highly diverse, underscoring the complexity of these neurodevelopmental disorders.
- Clinical exome sequencing is a valuable diagnostic tool for ASD, offering a viable alternative to whole-exome sequencing.
- Further research into variants of unknown significance is warranted to elucidate their role in ASD pathogenesis.
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