title: Application of Array Comparative Genomic Hybridization in Newborns with Multiple Congenital Anomalies.
abstract: Major congenital anomalies are detectable in 2-3 % of the newborn population. Some of their genetic causes are attributable to copy number variations identified by array comparative genomic hybridization (aCGH). The value of aCGH screening as a first-tier test in children with multiple congenital anomalies has been studied and consensus adopted. However, array resolution has not been agreed upon, specifically in the newborn or infant population. Moreover, most array studies have been focused on mixed populations of intellectual disability/developmental delay with or without multiple congenital anomalies, making it difficult to assess the value of microarrays in newborns. The aim of the study was to determine the optimal quality and clinical sensitivity of high-resolution array comparative genomic hybridization in neonates with multiple congenital anomalies. We investigated a group of 54 newborns with multiple congenital anomalies defined as two or more birth defects from more than one organ system. Cytogenetic studies were performed using OGT CytoSure 8 × 60 K microarray. We found ten rearrangements in ten newborns. Of these, one recurrent syndromic microduplication was observed, whereas all other changes were unique. Six rearrangements were definitely pathogenic, including one submicroscopic and five that could be seen on routine karyotype analysis. Four other copy number variants were likely pathogenic. The candidate genes that may explain the phenotype were discussed. In conclusion, high-resolution array comparative hybridization can be applied successfully in newborns with multiple congenital anomalies as the method detects a significant number of pathogenic changes, resulting in early diagnoses. We hypothesize that small changes previously considered benign or even inherited rearrangements should be classified as potentially pathogenic at least until a subsequent clinical assessment would exclude a developmental delay or dysmorphism.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland. krzysztof.szczaluba@gmail.com.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szczałuba
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Nowakowska
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sobecka
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Smyk
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Castaneda
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Klapecki
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kutkowska-Kaźmierczak
authors.affiliation: Department of Genetics, Wroclaw Medical University, Wroclaw, Poland.|Department of Social Pediatrics, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Śmigiel
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 17a Kasprzaka St., 01-211, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Bocian
authors.affiliation: Department of Immunopathology of Infectious and Parasitic Diseases, Warsaw Medical University, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Warsaw Medical University, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Demkow
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male
keywords: Array comparative genomic hybridization; Birth defects; Congenital anomalies; Copy number variants; Dysmorphism; Newborns; Phenotyping