The clinical utility of molecular karyotyping using high-resolution array-comparative genomic hybridization

Abstract

Clinical characteristics of patients are not always related to specific syndromes. Array-comparative genomic hybridization (aCGH) is used to detect submicroscopic copy number variants within the genome not visible by conventional karyotyping. The clinical application of aCGH has helped the genetic diagnosis of patients with unexplained developmental delay/intellectual disability, autism spectrum disorders, with or without multiple congenital anomalies. Since 2008, we have implemented aCGH with the 244K and 4 × 180K Agilent platform on 334 patients with various degrees of developmental delay/intellectual disability, seizures, autism spectrum disorders, multiple congenital anomalies and normal previous conventional karyotype. Many of the patients had also received a variety of other genetic tests (Fragile X syndrome, Rett syndrome, single FISH tests or metabolic screens), which were normal. Clinically significant submicroscopic imbalances with aCGH were detected in 84 (∼25.15%) patients. aCGH is proving to be a powerful tool for the identification of novel chromosomal syndromes, thus allowing accurate prognosis and phenotype-genotype correlations.

Array comparative genomic hybridization as a clinical diagnostic tool in syndromic and nonsyndromic congenital heart disease

“…In 14 patients, we identified known microdeletion and microduplication syndromes: DiGeorge (3), 1p36 microdeletion (3), 9q subtelomeric microduplication (3), Williams syndrome (2), CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital defect, Ear anomalies and/or deafness) (1), 17q21-31 microduplication (1), and Jacobsen syndrome (1) (Figure 1). In general, it is given that phenotypes of microduplications are milder as compared with those caused by microdeletions in the same chromosomal region; this was confirmed by our cases and previously published results (6).…”

“…The types of heart defect in each of the 37 patients with a pathogenic CNV detected are shown in Table 1. The assignment of CNVs pathogenicity was based on the gene content according to the University of California Santa Cruz Genome Browser database (http://genome.ucsc.edu/) human genome build 18 or 19 (6). In addition, these patients presented Congenital heart disease and array CGH Articles …”

“…The 4 × 180K platform is composed of >170,000 60-mer oligonucleotide probes with average spatial resolution of 13-25 kb (annotated against National Center for Biotechnology Information build 36, hg18, and National Center for Biotechnology Information build 37, hg19). An array CGH test was performed for each patient using the standardized protocol recommended by the manufacturer and as described previously (6). Slides were scanned with an Agilent microarray scanner G2565CA, software version 4.8.4.1.…”

JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse

“…We found that JAKMIP1 was differentially expressed in patients with two syndromic forms of ASD, Fragile X and (dup)15q11–13 syndrome, and upon RBFOX1 knockdown (Fogel et al, 2012; Nishimura et al, 2007). To date, eleven ASD subjects have been identified with copy number variations that contain JAKMIP1 (Autism Genome Project et al, 2007; Kaminsky et al, 2011; Poultney et al, 2013; Tzetis et al, 2012). But, its interactions or function in the CNS, especially during brain development, are largely unknown.…”

Application of high-resolution array comparative genomic hybridization in children with unknown syndromic microcephaly

“…High resolution 4x180K and 1x244K Agilent SurePrint G3 arrays (>170.000 and >236.000 probes respectively, average resolution >8.9Kb) were used in this study (Agilent Technologies, Santa Clara, CA, www.agilent.com). Labeling, hybridization and data processing was carried out according to the manufacturer's recommendations and as previously described (3). The benign CNVs (or CNPs) that are reported in the Database for Genomic Variants (http://dgv.tcag.ca/dgv/app/home) were removed from the results.…”