Abstract

We conducted a retrospective analytical study in order to determine the yield of currently available diagnostic testing for ASD at our academic medical genetics center (State University), where all genetic tests are send-out, and no institutional funding is available to cover the cost. The diagnostic laboratories were selected based on acceptance and authorization by the patient’s insurance plan. Therefore, the diagnostic studies were not universal, and not every patient had the same set of diagnostic testing. Still the overall diagnostic yield was 36.8% (39/106), which is greater than or equal to that of published studies. A total of 106 patients with autism spectrum disorder (ASD) from Appalachian region of Northeast Tennessee, and Southwest Virginia were retrospectively studied. The clinical presentations (phenotypes) were categorized to ASD-Simplex (no dysmorphic features), ASD-Complex (with dysmorphic features), Syndromic (confirmed by genetic tests), and Autistic behavior (not diagnosed as ASD by a psychologist). The male to female ratio in patients with abnormal test result was 3:1 for ASD-simplex, 2:1 for ASD- complex, and 2.83:1 for combined, not including syndromic group, as the ratio depends on the mode of inheritance of the identified syndrome. The primary diagnostic test was chromosome microarray (CMA) with pathogenic/Likely pathogenic results in 23% of patients (22 out of 95 patients who had CMA analysis) showed a copy number variant (CNV) of microdeletion/microduplication with the most frequent CNVs involved 7q11.22 and 16p11.2 chromosomes. Point mutations were identified in 14% (15), through ASD panels (4); whole exome sequencing (5); and syndromes’ single gene/panel (6) with each mutation found in a single patient except for PTEN mutations which was identified in 2 patients. Chromosome aneuploidy was identified in 2 patients (T21 and XXY).