title: Haploinsufficiency of the miR-873/miR-876 microRNA cluster is associated with craniofacial abnormalities.
abstract: MicroRNA haploinsufficiency has been associated with developmental defects in only a limited number of cases. Here we report a de novo genomic microdeletion that includes the LINGO2 gene as well as two microRNA genes, MIR873 and MIR876, in a patient with craniofacial abnormalities - in particular macrocephaly and hypertelorism - and learning difficulties. Subsequent analysis revealed that the microRNAs affected by this de novo microdeletion form a mammalian-lineage, neuronal tissue-enriched cluster. In addition, bioinformatic analysis and experimental data indicate that miR-873 is involved in the regulation of the Hedgehog signaling, an essential pathway involved in craniofacial patterning and differentiation. Collectively these observations are consistent with a role of the miR-873/miR-876 microRNA cluster in physiological cranial bone development and indicate that mutations affecting these microRNAs could be a rare cause of developmental defect in humans.
authors: Department of Cytogenetics and Genomics, The Cyprus institute of Neurology and Genetics, Cyprus.
authors: Costas
authors: C
authors: Koufaris
authors: Department of Biological Sciences, University of Cyprus, Cyprus.
authors: Gregoris
authors: G
authors: Papagregoriou
authors: Department of Cytogenetics and Genomics, The Cyprus institute of Neurology and Genetics, Cyprus.
authors: Ludmila
authors: L
authors: Kousoulidou
authors: Department of Cytogenetics and Genomics, The Cyprus institute of Neurology and Genetics, Cyprus.
authors: Maria
authors: M
authors: Moutafi
authors: Centre de référence du Syndrome de Prader-Willi, Unité d'endocrinologie, obésité, maladies osseuses, génétique et gynécologiqe médicale, Hôpital des enfants CHU Toulouse, France.
authors: Maithé
authors: M
authors: Tauber
authors: Centre de référence du Syndrome de Prader-Willi, Unité d'endocrinologie, obésité, maladies osseuses, génétique et gynécologiqe médicale, Hôpital des enfants CHU Toulouse, France.
authors: Béatrice
authors: B
authors: Jouret
authors: Unité d'endocrinologie, obésité, maladies osseuses, génétique et gynécologiqe médicale, Hôpital des enfants CHU Toulouse, France.
authors: Isabelle
authors: I
authors: Kieffer
authors: Department of Biological Sciences, University of Cyprus, Cyprus.
authors: Constantinos
authors: C
authors: Deltas
authors: Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, Cyprus.
authors: George A
authors: GA
authors: Tanteles
authors: Department of Clinical Genetics, Makarios Hospital, Cyprus.
authors: Violetta
authors: V
authors: Anastasiadou
authors: Translational Genetics Team, The Cyprus Institute of Neurology and Genetics, Cyprus.
authors: Philippos C
authors: PC
authors: Patsalis
authors: Department of Cytogenetics and Genomics, The Cyprus institute of Neurology and Genetics, Cyprus. Electronic address: csismani@cing.ac.cy.
authors: Carolina
authors: C
authors: Sismani
mesh_terms: D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics; D002460:Cell Line; D057895:Haploinsufficiency / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D006972:Hypertelorism / Q000235:genetics*; D007859:Learning Disabilities / Q000235:genetics; D058627:Megalencephaly / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D017385:Sequence Homology; D015398:Signal Transduction / Q000235:genetics; D012886:Skull / Q000196:embryology / Q000254:growth & development
chemical_list: D053823:Hedgehog Proteins; C000598459:MIRN873 microRNA, human; C000598700:MIRN876 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins
keywords: Craniofacial; Developmental defect; Haploinsufficiency; Hedgehog; miR-873; miR-876