Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients

Though whole exome sequencing is the gold standard for the diagnosis of neurodevelopmental disorders, it remains expensive for some genetic centers. Commercialized panels comprising all OMIM-referenced genes called "medical exome" constitute an alternative strategy to whole exome sequencing, but its efficiency is poorly known. In this study, we report the experience of two clinical genetic centers using medical exome for diagnosis of neurodevelopmental disorders.

We recruited 216 consecutive index patients with neurodevelopmental disorders in two French genetic centers, corresponded to the daily practice of the units and included non-syndromic intellectual disability (n=33), syndromic intellectual disability (n=122), pediatric neurodegenerative disorders (n=7) and autism spectrum disorder (n=54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit.

We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with intellectual disability as the main diagnosis (32%) than in patients with autism spectrum disorder (3.7%). Our results suggest that the use of medical exome is a valuable strategy for patients with intellectual disability when whole exome sequencing cannot be used as a routine diagnosis tool.

Graphical Abstract

TruSight One global diagnostic yield in 216 consecutive patients with neurodevelopmental disorder, negative for X fragile and chromosomal microarray from two French clinical genetic centers: 25.9%

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