title: A review of craniofacial disorders caused by spliceosomal defects.
abstract: The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.
authors: Department of Genetics, APHP, Hôpital Necker-Enfants Malades, Paris, France.
authors: D
authors: D
authors: Lehalle
authors: Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany.
authors: D
authors: D
authors: Wieczorek
authors: Departamento de Genetica Clinica, Hospital de Reabilitacao de Anomalias Craniofaciais, Universidade de Sao Paulo (HRAC-USP), Bauru, Brasil.
authors: R M
authors: RM
authors: Zechi-Ceide
authors: Centro de Estudos do Genoma Humano, Instituto de Biociencias, Universidade de Sao Paulo, Sao Paulo, Brasil.
authors: M R
authors: MR
authors: Passos-Bueno
authors: Department of Genetics, APHP, Hôpital Necker-Enfants Malades, Paris, France.|INSERM UMR 1163, Institut Imagine, Paris, France.|Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France.
authors: S
authors: S
authors: Lyonnet
authors: Department of Genetics, APHP, Hôpital Necker-Enfants Malades, Paris, France.|INSERM UMR 1163, Institut Imagine, Paris, France.|Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France.
authors: J
authors: J
authors: Amiel
authors: INSERM UMR 1163, Institut Imagine, Paris, France.|Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France.
authors: C T
authors: http://orcid.org/0000-0002-9300-8399
authors: CT
authors: Gordon
mesh_terms: D002754:Choanal Atresia / Q000235:genetics / Q000378:metabolism*; D003025:Clubfoot / Q000235:genetics / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000235:genetics; D003638:Deafness / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics; D019066:Facies; D005260:Female; D006228:Hand Deformities, Congenital / Q000235:genetics / Q000378:metabolism*; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000235:genetics / Q000378:metabolism*; D008844:Micrognathism / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010445:Peptide Elongation Factors / Q000235:genetics; D010855:Pierre Robin Syndrome / Q000235:genetics / Q000378:metabolism*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics; D017415:Ribonucleoprotein, U5 Small Nuclear / Q000235:genetics; D012272:Ribs / Q000002:abnormalities* / Q000378:metabolism; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism*
chemical_list: C581608:EFTUD2 protein, human; D010445:Peptide Elongation Factors; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D017415:Ribonucleoprotein, U5 Small Nuclear; C486347:SF3B4 protein, human; C506012:TXNL4A protein, human; D039601:Eukaryotic Initiation Factor-4A; C403493:EIF4A3 protein, human; D053487:DEAD-box RNA Helicases
keywords: congenital malformations; craniofacial; mandibulofacial dysostosis; spliceosome