Clinical genetic testing for patients with autism spectrum disorders

Area of Science:

• Genetics
• Neurodevelopmental Disorders

Background:

• Autism spectrum disorders (ASDs) have a significant genetic component.
• Current clinical genetic testing guidelines for ASD include karyotype and fragile X testing.
• Guidelines for chromosomal microarray analysis (CMA) in ASD diagnosis are not yet established.

Purpose of the Study:

• To compare the diagnostic yield of G-banded karyotype, fragile X DNA testing, and chromosomal microarray (CMA) for patients with autism spectrum disorder (ASD).
• To evaluate the utility of CMA in detecting submicroscopic genomic deletions and duplications in ASD patients.

Main Methods:

• A cohort of 933 patients diagnosed with ASD underwent clinical genetic testing.
• Tests included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA).
• The diagnostic yield of clinically significant genetic findings was compared across the different tests.

Main Results:

• Chromosomal microarray (CMA) identified copy-number variations in 18.2% of patients, significantly higher than karyotype (2.23%) and fragile X testing (0.46%).
• Clinically significant CMA findings were observed in 7.0% of patients, including known genomic disorders and variants of potential significance.
• Most copy-number changes detected by CMA were unique to individual patients, with exceptions for recurrent variants like 16p11.2 and 15q13.2q13.3.

Conclusions:

• Chromosomal microarray (CMA) demonstrates the highest detection rate for genetic abnormalities in patients with autism spectrum disorder (ASD).
• Interpreting CMA data can be challenging due to novel and recurrent copy-number variants of unknown significance.
• CMA is recommended as a component of the initial diagnostic evaluation for individuals with ASD.