title: 13q31.1 microdeletion: A prenatal case report with macrocephaly and macroglossia.
abstract: We report on a female fetus with macrocephaly and macroglossia harbouring 13q31.1 microdeletion encompassing three genes: SPRY2, NDFIP2 and RBM26. NDFIP2 protein is involved in ubiquitination and in Ras/mitogen-activated protein kinase (MAPK) signaling pathways. SPRY2 protein is part of Sprout protein family and inhibits the Ras/MAPK pathways. Ras/MAPK pathway plays important role in complex cellular programs including cell differentiation and proliferation. Germline mutations in genes encoding protein involved in the MAPK cascade is responsible for a wide family of developmental disorders known as RASopathies. Some RASopathies, such as Costello syndrome, present a phenotype with (relative) macrocephaly as perinatal features. However, prenatal-onset macroglossia are generally absent in this syndrome but rather suggestive of the Beckwith-Wiedemann syndrome for which molecular testing were negative. Phenotype-genotype correlation with patients from DECIPHER defines NDFIP2 and SPRY2 as a possible candidate genes for a RASopathy potentially responsible for the clinical features in the fetus. Finally, this original case of 13q31.1 microdeletion underlines the importance of array-CGH in prenatal diagnosis with sonographic signs such as macroglossia and/or macrocephaly. In this case, genetic investigation should be not limited to the search of well-known genetic causes and other genomic microdeletions should be considered as alternative diagnoses for macroglossia.
authors.affiliation: Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38043 Grenoble Cedex, France; Université Grenoble-Alpes, 38000 Grenoble, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Poreau
authors.affiliation: Université Grenoble-Alpes, 38000 Grenoble, France; CHU Grenoble, 38043 Grenoble Cedex, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lin
authors.affiliation: Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38043 Grenoble Cedex, France; Université Grenoble-Alpes, 38000 Grenoble, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bosson
authors.affiliation: Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38043 Grenoble Cedex, France; Université Grenoble-Alpes, 38000 Grenoble, France; Inserm U836, Equipe 4, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dieterich
authors.affiliation: Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38043 Grenoble Cedex, France; Université Grenoble-Alpes, 38000 Grenoble, France; Equipe "Genetics Epigenetics and Therapies of Infertility" Institut Albert Bonniot, INSERM U823, La Tronche F-38706, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Satre
authors.affiliation: Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38043 Grenoble Cedex, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Devillard
authors.affiliation: Service de Gynécologie-Obstétrique, Hôpital Couple-Enfant, CHU Grenoble, Grenoble, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Guigue
authors.affiliation: Université Grenoble-Alpes, 38000 Grenoble, France; CHU Grenoble, 38043 Grenoble Cedex, France.
authors.forename: Candice
authors.initials: C
authors.lastname: Ronin
authors.affiliation: Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38043 Grenoble Cedex, France; Université Grenoble-Alpes, 38000 Grenoble, France; Inserm U1036, biologie du cancer et de l'infection, iRTSV, CEA Grenoble, 17, rue des Martyrs, 38054 Grenoble Cedex 9, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouillet
authors.affiliation: Centre d'échographie, 38500 Voiron, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Barbier
authors.affiliation: Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38043 Grenoble Cedex, France; Université Grenoble-Alpes, 38000 Grenoble, France; UMR CNRS 5525 TIMC-IMAG, équipe DYCTIM, CHU Grenoble, Grenoble, France.
authors.forename: Pierre-Simon
authors.initials: PS
authors.lastname: Jouk
authors.affiliation: Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38043 Grenoble Cedex, France; Université Grenoble-Alpes, 38000 Grenoble, France; Equipe "Genetics Epigenetics and Therapies of Infertility" Institut Albert Bonniot, INSERM U823, La Tronche F-38706, France. Electronic address: ccoutton@chu-grenoble.fr.
authors.forename: Charles
authors.initials: C
authors.lastname: Coutton
mesh_terms: D000328:Adult; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008260:Macroglossia / Q000175:diagnosis / Q000235:genetics*; D058627:Megalencephaly / Q000175:diagnosis / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D011247:Pregnancy; D013577:Syndrome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C477747:NDFIP2 protein, human; C485561:SPRY2 protein, human
keywords: 13q31.1 microdeletion; Array-CGH; Macrocephaly; Macroglossia; NDFIP2; Prenatal diagnosis; Rasopathies; SPRY2