title: Clinical and molecular characterization of an infant with a tandem duplication and deletion of 19p13.
abstract: Copy number variations (CNVs) on the short arm of chromosome 19 are relatively rare. We present a patient with a tandem de novo 3.9 Mb duplication of 19p13.12p13.2 and an adjacent 288 kb deletion of 19p13.12. The CNVs were detected by genome wide SNP-array and confirmed by fluorescence in situ hybridization. Mate-pair sequencing revealed two breakpoint junctions leading to a germline tandem inverted duplication and an adjacent deletion. The patient had a major congenital heart defect and refractory edema leading to metabolic and endocrinological disturbances. Further complications occurred due to refractory chylothorax, severe inflammatory response syndrome, and repeating sepsis. After 2 months, the child died due to intractable respiratory failure. The phenotype of this patient was compared with reported patients with overlapping deletions or duplications. We conclude that the congenital heart defect, respiratory insufficiency, and abnormal neurologic examination are most likely due the contiguous gene deletion/duplication.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ratna N G B
authors.initials: RN
authors.lastname: Tan
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ruben S G M
authors.initials: RS
authors.lastname: Witlox
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hilhorst-Hofstee
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Cacha M P C D
authors.initials: CM
authors.lastname: Peeters-Scholte
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Nicolette S
authors.initials: NS
authors.lastname: den Hollander
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Claudia A L
authors.initials: CA
authors.lastname: Ruivenkamp
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Mariëtte J V
authors.initials: MJ
authors.lastname: Hoffer
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Kerstin B
authors.initials: KB
authors.lastname: Hansson
authors.affiliation: Center for Molecular Medicine, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: van Roosmalen
authors.affiliation: Center for Molecular Medicine, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Wigard P
authors.initials: WP
authors.lastname: Kloosterman
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Gijs W E
authors.initials: GW
authors.lastname: Santen
mesh_terms: D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002888:Chromosomes, Human, Pair 19; D006801:Humans; D007231:Infant, Newborn; D008297:Male
keywords: chromosome 19 duplication and deletion; congenital heart disease; mate-pair sequencing; refractory edema