title: High-resolution molecular karyotyping in patients with developmental delay and/or multiple congenital anomalies in a clinical setting.
abstract: Microarray-based comparative genomic hybridization (array-CGH) enables genomewide investigation of copy-number changes at high resolution and has recently been implemented as a clinical diagnostic tool. In this study we evaluate the usefulness of high-resolution arrays as a diagnostic tool in our laboratory and investigate the diagnostic yield in the first 160 patients who were clinically referred for investigation of developmental delay (DD)/multiple congenital anomalies (MCA). During this period both 38K BAC-arrays and 244K oligonucleotide-arrays were used. Copy-number variations (CNVs) not previously reported as normal variants were detected in 22.5% of cases. In 13.1% the aberrations were considered causal to the phenotype and in 9.4% the clinical significance was uncertain. There was no difference in diagnostic yield between patients with mild, moderate or severe DD. Although the effective resolution of the 244K oligonucleotide-arrays was higher than the 38K BAC-array, the diagnostic yield of both platforms was approximately equal and no causal aberrations <300 kb were detected in this patient cohort. We experienced that increasing the resolution of a whole genome screen in the diagnostic setting has its drawback of detecting an increased number of CNVs with uncertain contribution to a phenotype. Based on our experiences, array-CGH is recommended as the first-step analysis in the genetic evaluation of patients with DD and/or MCA.
authors.affiliation: Department of Molecular Medicine and Surgery and Center for Molecular Medicine, CMM L8:02, Karolinska Institutet, Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden. Josephine.Wincent@ki.se
authors.forename: J
authors.initials: J
authors.lastname: Wincent
authors.forename: B-M
authors.initials: BM
authors.lastname: Anderlid
authors.forename: M
authors.initials: M
authors.lastname: Lagerberg
authors.forename: M
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: J
authors.initials: J
authors.lastname: Schoumans
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping / Q000379:methods; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D020411:Oligonucleotide Array Sequence Analysis; D012720:Severity of Illness Index; D055815:Young Adult