title: Complex translocation t(1;12;14)(q42;q14;q32) and HMGA2 deletion in a fetus presenting growth delay and bilateral cataracts.
abstract: We report the prenatal detection of a de novo unbalanced complex chromosomal rearrangement (CCR), in a fetus with growth delay and bilateral cataracts. Standard karyotype and FISH analyses on amniotic fluid revealed a complex de novo translocation, resulting in a 46,XY,t(1;12;14)(q42;q14;q32) karyotype. CGH-array showed a significant deletion of 387  kb at 12q14.3, at a distance of only 200-700 kb from the breakpoint at 12q14, which encompassed the HMGA2 gene and occurred de novo. Although 12q14 microdeletions are associated with growth delay in several reports in the literature, we present here the smallest deletion prenatally detected, and we detail the clinical description of the fetus. The correlation between cataracts and this complex genotype is puzzling. Among the genes disrupted by the breakpoint in 12q14, GRIP1 has been associated with abnormal eye development in mice, including lens degeneration. Interestingly, HMGA2 is expressed in the mouse's developing lens, and its expression is decreased in lens of elderly humans, correlated with the severity of lens opacity. In this report, we refine the link between HMGA2 loss of function and growth delay during prenatal development. We also discuss the correlation between cataracts and genotype in this unbalanced CCR case of unexpected complexity.
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Raymond
authors.affiliation: Génétique moléculaire, Pharmacogénétique et Hormonologie, Hôpital Bicêtre, APHP, Le Kremlin-Bicêtre, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Francou
authors.affiliation: Génétique Moléculaire, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France.
authors.forename: François
authors.initials: F
authors.lastname: Petit
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France; INSERM U935, Villejuif, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Tosca
authors.affiliation: Service de Biochimie-Génétique, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, APHP, 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: Service de Biochimie-Génétique, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, APHP, Créteil, France; INSERM U955, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, Créteil, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Metay
authors.affiliation: Unité de Fœtopathologie, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France.
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinovic
authors.affiliation: Service de Gynécologie Obstétrique, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France.
authors.forename: Anne-Gaël
authors.initials: AG
authors.lastname: Cordier
authors.affiliation: Service de Gynécologie Obstétrique, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benachi
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Pineau
authors.affiliation: Génétique moléculaire, Pharmacogénétique et Hormonologie, Hôpital Bicêtre, APHP, Le Kremlin-Bicêtre, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.affiliation: Service de Biochimie-Génétique, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, APHP, Créteil, France; INSERM U955, Plateforme de Génétique Constitutionnelle, Hôpital H. Mondor, Créteil, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France; INSERM U935, Villejuif, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Tachdjian
authors.affiliation: Service d'Histologie-Embryologie-Cytogénétique, Hôpitaux Universitaires Paris-Sud, Site Antoine Béclère, APHP, Clamart, France. Electronic address: sophie.brisset@abc.aphp.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brisset
mesh_terms: D000328:Adult; D002386:Cataract / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D056905:Chromosome Breakpoints; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging / Q000235:genetics*; D017353:Gene Deletion; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D011247:Pregnancy; D013577:Syndrome; D014178:Translocation, Genetic; D014463:Ultrasonography
chemical_list: D025743:HMGA2 Protein
keywords: Cataracts; Complex chromosomal rearrangement; Fetal growth delay; HMGA2