title: Refining the phenotypical and mutational spectrum of Taybi-Linder syndrome.
abstract: Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non-coding small nuclear RNA which is a critical component of the minor spliceosome. We report here four foetuses and four unrelated patients with RNU4ATAC mutations. We provide antenatal descriptions of this rare syndrome including unusual features found in two twin foetuses with compound heterozygosity for two rare mutations who presented with mild intrauterine growth retardation and atypical dysmorphic facial features. We also carried out a literature review of the patients described up to now with RNU4ATAC mutations, affected either with TALS or Roifman syndrome, a recently described allelic disorder.
authors.affiliation: Service de Génétique, Hospices Civils de Lyon, Lyon, France.|Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Putoux
authors.affiliation: Service de Génétique, Hospices Civils de Lyon, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Alqahtani
authors.affiliation: Département de Génétique Médicale, Centre Hospitalier Universitaire, Montpellier, France.
authors.forename: L
authors.initials: L
authors.lastname: Pinson
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands.|School for Oncology & Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: A D C
authors.initials: AD
authors.lastname: Paulussen
authors.affiliation: Service de Génétique, Hospices Civils de Lyon, Lyon, France.
authors.forename: J
authors.initials: J
authors.lastname: Michel
authors.affiliation: Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Besson
authors.affiliation: Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Mazoyer
authors.affiliation: Department of Pathology, University of Malta, Medical Genetics Unit, Mater Dei Hospital, Malta.
authors.forename: I
authors.initials: I
authors.lastname: Borg
authors.affiliation: Department of Paediatric Genetics, Amrita Institute of Medical Sciences and Research Centre, Cochin, India.
authors.forename: S
authors.initials: S
authors.lastname: Nampoothiri
authors.affiliation: Centre de Pathologie et Neuropathologie Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Vasiljevic
authors.affiliation: Centre for Medical Genetics, College of Medicine and Health Sciences, University of Rwanda, Huye, Rwanda.
authors.forename: A
authors.initials: A
authors.lastname: Uwineza
authors.affiliation: Service de Génétique, Hospices Civils de Lyon, Lyon, France.
authors.forename: D
authors.initials: D
authors.lastname: Boggio
authors.affiliation: Service de Gynécologie-Obstétrique, Hospices Civils de Lyon, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Champion
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands.|School for Oncology & Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: C E
authors.initials: CE
authors.lastname: de Die-Smulders
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Gardeitchik
authors.affiliation: Paediatric Intensive Care Unit, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: W K
authors.initials: WK
authors.lastname: van Putten
authors.affiliation: Département de Génétique Médicale, Unité de fœtopathologie, Centre Hospitalier Universitaire, Montpellier, France.
authors.forename: M J
authors.initials: MJ
authors.lastname: Perez
authors.affiliation: Département de Pathologie Tissulaire et Cellulaire des tumeurs, Pôle Biologie Pathologie, Centre Hospitalier Universitaire, Montpellier, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Musizzano
authors.affiliation: Département de Génétique Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfant Malade, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Razavi
authors.affiliation: Department of Genetics, APHP-Robert DEBRE University Hospital, and Paris-Diderot University, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Drunat
authors.affiliation: Department of Genetics, APHP-Robert DEBRE University Hospital, and Paris-Diderot University, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Verloes
authors.affiliation: Department of Paediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Hennekam
authors.affiliation: Département d'Imagerie Pédiatrique et Fœtale, Centre Pluridisciplinaire de Diagnostic Prénatal, Hôpital Femme Mère Enfant, Lyon-Bron, France.
authors.forename: L
authors.initials: L
authors.lastname: Guibaud
authors.affiliation: Service de Génétique, Hospices Civils de Lyon, Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Alix
authors.affiliation: Service de Génétique, Hospices Civils de Lyon, Lyon, France.|Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: D
authors.initials: D
authors.lastname: Sanlaville
authors.affiliation: Service de Génétique, Hospices Civils de Lyon, Lyon, France.|Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Lesca
authors.affiliation: Service de Génétique, Hospices Civils de Lyon, Lyon, France.|Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Edery
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000483:Alleles; D009202:Cardiomyopathies / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004392:Dwarfism / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000503:physiopathology; D005333:Fetus; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000503:physiopathology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008831:Microcephaly / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D000081207:Primary Immunodeficiency Diseases; D012342:RNA, Small Nuclear / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics* / Q000503:physiopathology; D017381:Spliceosomes / Q000235:genetics
chemical_list: D012342:RNA, Small Nuclear; C000590616:RNU4ATAC RNA, human
keywords: RNU4ATAC; Taybi-Linder syndrome; corpus callosum agenesis; dwarfism; microcephalic osteodysplastic primordial dwarfisms; microcephaly; spliceosome