2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-The utility of exome sequencing for neurodevelopmental disorders at a large reference laboratory

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A study conducted at a large reference laboratory evaluated the utility of exome sequencing (ES) for neurodevelopmental disorders (ND). The study included a cohort of consecutive patients for whom ES was ordered for ND or other indications. The results showed that ES had a lower overall positivity rate for ND samples (21.5%) compared to previous studies. There was a significant difference in positivity rate between ND and non-ND samples, with ND samples having a lower positivity rate. However, there was no significant difference in result category between proband-only and trio samples.<br /><br />The study analyzed a total of 652 ES results, with 43.6% being proband-only samples, 12.0% duo samples, and 44.5% trio samples. The most common indication for testing was developmental delay and/or intellectual disability. The result categories were positive (19.5%), variant of uncertain significance (VUS) (26.4%), and negative (54.1%).<br /><br />Among samples with ND indication, there was no significant difference in result category between proband-only and trio samples. However, compared to samples with non-ND indication, those with ND indication had a significantly lower rate of positive results and a higher rate of negative results.<br /><br />The study has some limitations, including limited clinical information for testing indication in some cases and a limited definition of ND that did not include other behavioral abnormalities or mental health diagnoses. The authors suggest that future research could consider including a larger sample size, broadening the definition of ND test indications, evaluating the number of ND test indications for each ND sample, and analyzing the de novo rate for positive trio samples.

Asset Subtitle

Presenting Author - Kailey M. Owens, MS, CGC; Co-Author - Jonathon R. Lutz, BS; Co-Author - Zoe Powis, MS;

Meta Tag

Cognitive Disorders

Exome sequencing

Genetic Testing

Intellectual disability

NextGen Sequencing

Co-Author Jonathon R. Lutz, BS

Co-Author Zoe Powis, MS

Presenting Author Kailey M. Owens, MS, CGC

Keywords

exome sequencing

neurodevelopmental disorders

positivity rate

proband-only samples

trio samples

indication for testing

developmental delay

intellectual disability

variant of uncertain significance

negative results