Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature
| Autor: | Matthieu P. Robert, Salima El Chehadeh, Geert Vandeweyer, Candace Bensignor, Wilhelmina S. Kerstjens-Frederikse, Darina Prchalova, Hélène Dollfus, Jean-Baptiste Rivière, Christel Thauvin-Robinet, Paul Kuentz, Edwin Reyniers, Patrick Calvas, Caroline Bonnet, Marketa Havlovicova, Rodica Isaiko, Vincent Laugel, Nicolas Chassaing, Julien Thevenon, Christian Gilissen, Morgane Straub, Laurence Faivre, Yannis Duffourd, Miroslava Hancarova, Bart Loeys, R. Frank Kooy, Ange-Line Bruel, Rolph Pfundt, Catherine Creuzot-Garcher, Jolien S. Klein Wassink-Ruiter, Zdenek Sedlacek |
|---|---|
| Přispěvatelé: | FHU TRANSLAD, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Génétique des Anomalies du Développement ( GAD ), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne ( UB ), Service de pédiatrie (CHU de Dijon), Service d'Ophtalmologie (CHU de Dijon), Service de Cardiologie (hôpital général, CHU Dijon), Hôpital général (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), FHU TRANSLAD (CHU de Dijon), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Service de Cardiologie, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male MESH: Heart Defects Congenital / physiopathology Microcephaly Pathology MESH: Heart Defects Congenital / genetics MESH: Exome / genetics 030105 genetics & heredity MESH: RNA Splicing / genetics Microphthalmia [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Child Exome MESH: RNA Splicing Factors / genetics Child Frameshift Mutation MESH: High-Throughput Nucleotide Sequencing Genetics (clinical) Exome sequencing Coloboma MESH: Frameshift Mutation High-Throughput Nucleotide Sequencing Microdeletion syndrome Microcephaly Verheij syndrome PUF60 Chemistry Phenotype Child Preschool DISEASES Medical genetics Female RNA Splicing Factors medicine.symptom Chromosome Deletion Chromosomes Human Pair 8 MESH: Dwarfism / genetics Heart Defects Congenital medicine.medical_specialty GENES Adolescent RNA Splicing MESH: Chromosome Deletion Dwarfism Biology MESH: Phenotype Short stature Article PUF60 03 medical and health sciences Internal medicine Intellectual Disability [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology Genetics medicine Humans Craniofacial MESH: Adolescent Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] MESH: Humans MESH: Child Preschool medicine.disease MESH: Repressor Proteins / genetics MESH: Male Repressor Proteins 030104 developmental biology Endocrinology MESH: Chromosomes Human Pair 8 / genetics MESH: Dwarfism / physiopathology MESH: Intellectual Disability / physiopathology Human medicine MESH: Intellectual Disability / genetics Verheij syndrome MESH: Female [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | European Journal of Human Genetics, 25(1), 43-51. Nature Publishing Group European Journal of Human Genetics, 25, 43-51 European journal of human genetics: EJHG European journal of human genetics: EJHG, Nature, 2016, 25 (1), pp.43-51. 〈http://www.nature.com/ejhg/index.html〉. 〈10.1038/ejhg.2016.133〉 European Journal of Human Genetics European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (1), pp.43-51. ⟨10.1038/ejhg.2016.133⟩ European Journal of Human Genetics, Nature Publishing Group, 2016, 25 (1), pp.43-51. ⟨10.1038/ejhg.2016.133⟩ European journal of human genetics European Journal of Human Genetics, 25, 1, pp. 43-51 |
| ISSN: | 1018-4813 1476-5438 |
| Popis: | Item does not contain fulltext Verheij syndrome, also called 8q24.3 microdeletion syndrome, is a rare condition characterized by ante- and postnatal growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, developmental delay (DD), cardiac and renal defects and dysmorphic features. Recently, PUF60 (Poly-U Binding Splicing Factor 60 kDa), which encodes a component of the spliceosome, has been discussed as the best candidate gene for the Verheij syndrome phenotype, regarding the cardiac and short stature phenotype. To date, only one patient has been reported with a de novo variant in PUF60 that probably affects function (c.505C>T leading to p.(His169Tyr)) associated with DD, microcephaly, craniofacial and cardiac defects. Additional patients were required to confirm the pathogenesis of this association and further delineate the clinical spectrum. Here we report five patients with de novo heterozygous variants in PUF60 identified using whole exome sequencing. Variants included a splice-site variant (c.24+1G>C), a frameshift variant (p.(Ile136Thrfs*31)), two nonsense variants (p.(Arg448*) and p.(Lys301*)) and a missense change (p.(Val483Ala)). All six patients with a PUF60 variant (the five patients of the present study and the unique reported patient) have the same core facial gestalt as 8q24.3 microdeletions patients, associated with DD. Other findings include feeding difficulties (3/6), cardiac defects (5/6), short stature (5/6), joint laxity and/or dislocation (5/6), vertebral anomalies (3/6), bilateral microphthalmia and irido-retinal coloboma (1/6), bilateral optic nerve hypoplasia (2/6), renal anomalies (2/6) and branchial arch defects (2/6). These results confirm that PUF60 is a major driver for the developmental, craniofacial, skeletal and cardiac phenotypes associated with the 8q24.3 microdeletion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink