title: Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations.
abstract: We report paternally inherited duplication of 1q12q21.2 of 5.8 Mb associated with maternally inherited deletion of 16p11.2 of 545 Kb, this latter first identified in a fetus exhibiting an absent nasal bone detected during pregnancy. During the neonatal period, the young boy presented developmental delay, epilepsy, congenital anomalies and overweight. The clinical features of the proband with two rearrangements were more severe than in either of the parents carrying only one or the other mutation. Thus our data support a two-hit model in which the concomitant presence of these two copy-number variations exacerbates the neurodevelopmental phenotype.
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpital Antoine Béclère, Clamart, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brisset
authors.affiliation: AP-HP, Département de Génétique, CHU Robert Debré, Paris, France.
authors.forename: Yline
authors.initials: Y
authors.lastname: Capri
authors.affiliation: AP-HP, Service de Biochimie-Génétique, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, Créteil, France; INSERM U955, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, Créteil, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Briand-Suleau
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpital Antoine Béclère, Clamart, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Tosca
authors.affiliation: AP-HP, Département de Neuropédiatrie, CHU Robert Debré, Paris, France.
authors.forename: Domitille
authors.initials: D
authors.lastname: Gras
authors.affiliation: AP-HP, Département de Génétique, CHU Robert Debré, Paris, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Fauret-Amsellem
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpital Antoine Béclère, Clamart, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Pineau
authors.affiliation: AP-HP, Gynécologie Obstétrique, Hôpital Antoine Béclère, Clamart, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Saada
authors.affiliation: AP-HP, Service de Biochimie-Génétique, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, Créteil, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Ortonne
authors.affiliation: AP-HP, Département de Génétique, CHU Robert Debré, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.affiliation: AP-HP, Service de Biochimie-Génétique, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, Créteil, France; INSERM U955, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, Créteil, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpital Antoine Béclère, Clamart, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Tachdjian
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpital Antoine Béclère, Clamart, France; AP-HP, Service de Biochimie-Génétique, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, Créteil, France. Electronic address: corinne.metay@aphp.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Métay
mesh_terms: D002675:Child, Preschool; D002869:Chromosome Aberrations; D058674:Chromosome Duplication; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009295:Nasal Bone / Q000002:abnormalities; D010641:Phenotype
keywords: 16p11.2 deletion; 1q21.1q21.2 duplication; Two-hit case