講演情報
[OE4-5]Recommended First Tier Genetic Testing for Patients with Neurodevelopmental Disorders has Diagnostic Utility
○Aradhya Swaroop, McKnight Dianalee, Morales Ana, Finley Jenna, Hatchell Kathryn (Invitae Inc., San Francisco, USA)
OBJECTIVE:
We evaluated the diagnostic utility of AAP’s 2020 recommendations for utilizing chromosomal microarray (CMA) and FMR1 repeat expansion for patients with intellectual disability (ID), global developmental delay (DD), and/or autism followed by a gene panel (or exome) for patients with ID or DD. Collectively, these patients have a neurodevelopmental disorder (NDD).
METHODS:
The diagnostic yields of CMA (n=14,292), FMR1 repeat expansion (n=1,947), and an NGS deletion/duplication panel with 241 genes associated with NDD (NDD-panel, n=270) were assessed for patients with NDD.
RESULTS:
The diagnostic yield of CMA for patients with NDD was 10.4%, highest for those with ID (20.8%), followed by DD (14.0%) and autism (6.3%). FMR1 testing had a yield of 0.6%; 1.0% for patients with DD/ID and 0.4% for patients with autism. The NDD-panel had an overall yield of 12.6% and highest for patients with ID (18.4%), followed by DD (16.4%) and autism (5.3%). Twelve percent of NDD-panel positive cases had 1-2 exon deletions that may have been missed by the CMA and exome due to their small size.
CONCLUSIONS:
The overall combined yield of utilizing CMA, FMR1, and a NDD panel for patients with NDD was ~one in four. Depending on a patient’s clinical presentation, the combined yield ranged from ~40% for individuals with ID and ~10% with autism. Previously, researchers determined that 87% of patients with a genetically diagnosed DD had positive outcomes including: reproductive decision making, referrals to medical specialties, access to relevant patient information/groups, and disease-specific treatments.
We evaluated the diagnostic utility of AAP’s 2020 recommendations for utilizing chromosomal microarray (CMA) and FMR1 repeat expansion for patients with intellectual disability (ID), global developmental delay (DD), and/or autism followed by a gene panel (or exome) for patients with ID or DD. Collectively, these patients have a neurodevelopmental disorder (NDD).
METHODS:
The diagnostic yields of CMA (n=14,292), FMR1 repeat expansion (n=1,947), and an NGS deletion/duplication panel with 241 genes associated with NDD (NDD-panel, n=270) were assessed for patients with NDD.
RESULTS:
The diagnostic yield of CMA for patients with NDD was 10.4%, highest for those with ID (20.8%), followed by DD (14.0%) and autism (6.3%). FMR1 testing had a yield of 0.6%; 1.0% for patients with DD/ID and 0.4% for patients with autism. The NDD-panel had an overall yield of 12.6% and highest for patients with ID (18.4%), followed by DD (16.4%) and autism (5.3%). Twelve percent of NDD-panel positive cases had 1-2 exon deletions that may have been missed by the CMA and exome due to their small size.
CONCLUSIONS:
The overall combined yield of utilizing CMA, FMR1, and a NDD panel for patients with NDD was ~one in four. Depending on a patient’s clinical presentation, the combined yield ranged from ~40% for individuals with ID and ~10% with autism. Previously, researchers determined that 87% of patients with a genetically diagnosed DD had positive outcomes including: reproductive decision making, referrals to medical specialties, access to relevant patient information/groups, and disease-specific treatments.