title: Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications.
abstract: Karyotyping and aCGH are routinely used to identify genetic determinants of major congenital malformations (MCMs) in fetal deaths or terminations of pregnancy after prenatal diagnosis. Pathogenic rearrangements are found with a variable rate of 9-39% for aCGH. We collected 33 fetuses, 9 with a single MCM and 24 with MCMs involving 2-4 organ systems. aCGH revealed copy number variants in 14 out of 33 cases (42%). Eight were classified as pathogenic which account for a detection rate of 24% (8/33) considering fetuses with 1 or more MCMs and 33% (8/24) taking into account fetuses with multiple malformations only. Three of the pathogenic variants were known microdeletion syndromes (22q11.21 deletion, central chromosome 22q11.21 deletion, and TAR syndrome) and 5 were large rearrangements, adding up to >11 Mb per subject and comprising strong phenotype-related genes. One of those was a de novo complex rearrangement, and the remaining 4 duplications and 2 deletions were 130-900 kb in size, containing 1-7 genes, and were classified as variants of unknown clinical significance. Our study confirms aCGH as a powerful technique to ascertain the genetic etiology of fetal major congenital malformations.
authors.affiliation: Department of Medical Sciences, University of Torino, Turin, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Di Gregorio
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gai
authors.forename: Giovanni
authors.initials: G
authors.lastname: Botta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Calcia
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pappi
authors.forename: Flavia
authors.initials: F
authors.lastname: Talarico
authors.forename: Elisa
authors.initials: E
authors.lastname: Savin
authors.forename: Marisa
authors.initials: M
authors.lastname: Ribotta
authors.forename: Andrea
authors.initials: A
authors.lastname: Zonta
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mancini
authors.forename: Elisa
authors.initials: E
authors.lastname: Giorgio
authors.forename: Simona
authors.initials: S
authors.lastname: Cavalieri
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Ferrero
authors.forename: Elsa
authors.initials: E
authors.lastname: Viora
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasini
authors.forename: Enrico
authors.initials: E
authors.lastname: Grosso
authors.forename: Alfredo
authors.initials: A
authors.lastname: Brusco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Brussino
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D001344:Autopsy; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D055028:Comparative Genomic Hybridization / Q000706:statistics & numerical data*; D056915:DNA Copy Number Variations; D005260:Female; D005333:Fetus; D005838:Genotype; D006801:Humans; D007621:Karyotyping; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000706:statistics & numerical data