A Synopsis of Chromosomal Microarray Cases at Dartmouth‐Hitchcock Medical Center

Abstract

BackgroundChromosomal microarrays (CMA) used to assess DNA copy number are currently considered first‐tier clinical diagnostic tests for postnatal evaluation of individuals with intellectual disability (ID), developmental delay (DD), autism spectrum disorders (ASD), and/or multiple congenital anomalies (MCA). Here, we provide a summary of the CMA cases performed at Dartmouth‐Hitchcock Medical Center during the first month that clinical CMA testing was offered.MethodsWe used the CytoScan®HD microarray containing 750,000 SNP probes and 1.9 million non‐polymorphic probes with an average intragenic spacing of 880 base pairs and 384 base pairs for 340 genes recommended by the International Standards for Cytogenomic Array (ISCA) consortium. Several databases of copy number variants were used during interpretation including ISCA, OMIM, DECIPHER and the Database of Genomic Variants (DGV).Results16 cases (9 females and 5 males) with an average age of ~7yrs were analyzed and reported. The clinical indication for testing in 14/16 cases (87.5%) was ID, DD or ASD. Clinically significant copy number variants were detected and reported in 3/16 cases, a diagnostic yield of 18.75%. Additionally, two variants of uncertain significance (VOUS) were also reported in two cases with unexplained developmental delay.ConclusionsDespite the small number of cases, our diagnostic yield matches the well‐established CMA yield (15–20%) for genetic testing of individuals with ID, DD, ASD or MCA. This further emphasizes the fact that CMA provides higher sensitivity compared to G‐banded karyotyping albeit with the slight disadvantage of increased VOUS detection.