title: Rodriguez acrofacial dysostosis is caused by apparently de novo heterozygous mutations in the SF3B4 gene.
abstract: Acrofacial dysostosis syndrome of Rodriguez is characterized by severe mandibular underdevelopment, upper limb phocomelia with absent fingers, absent fibulae, cleft palate, microtia, and abnormal pulmonary function. First reported in three siblings it was assumed to be an autosomal recessive condition. However, subsequent publication reported a further five simplex occurrences and a living patient with a heterozygous mutation in the SF3B4 gene. Exome sequencing was performed on four fetuses with this disorder, including one of the originally described affected siblings. We identified two heterozygous frameshift mutations in the SF3B4 gene in three of the four fetuses investigated. The observed mutation was apparently de novo in one fetus for whom parental DNA was available. Thus, Acrofacial dysostosis syndrome of Rodriguez is an autosomal dominant condition and the recurrences identified in the initial report were likely due to gonadal mosaicism. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Clinical Genetics, Guy's Hospital, London, United Kingdom.|Division of Medical and Molecular Genetics, King's College London, London, United Kingdom.
authors.forename: Melita D
authors.initials: MD
authors.lastname: Irving
authors.affiliation: Division of Medical and Molecular Genetics, King's College London, London, United Kingdom.
authors.forename: Boyan I
authors.initials: BI
authors.lastname: Dimitrov
authors.affiliation: Department of Obstetrics and Gynaecology, University Dijkzigt, Rotterdam, The Netherlands.
authors.forename: Marja
authors.initials: M
authors.lastname: Wessels
authors.affiliation: Department of Clinical Genetics, Guy's Hospital, London, United Kingdom.
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.affiliation: The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, The University of Toronto, Toronto, Ontario, Canada.|Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sickkids, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.affiliation: Division of Medical and Molecular Genetics, King's College London, London, United Kingdom.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Simpson
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D005333:Fetus; D020022:Genetic Predisposition to Disease; D006228:Hand Deformities, Congenital / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D000072260:RNA Splicing Factors / Q000235:genetics*; D035781:Siblings
chemical_list: D000072260:RNA Splicing Factors; C486347:SF3B4 protein, human
keywords: Nager syndrome; Rodriguez acrofacial dysostosis; SF3B4; exome sequencing