title: Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.
abstract: Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.
authors.affiliation: Clinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: S R F
authors.initials: SR
authors.lastname: Twigg
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: L B
authors.initials: LB
authors.lastname: Ousager
authors.affiliation: Clinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Miller
authors.affiliation: Clinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Human Genomics Center, Faculty of Medicine and Pharmacy of Rabat, Rabat, Morocco.|Department of Medical Genetics, National Institute of Health, Rabat, Morocco.
authors.forename: S C
authors.initials: SC
authors.lastname: Elalaoui
authors.affiliation: Human Genomics Center, Faculty of Medicine and Pharmacy of Rabat, Rabat, Morocco.|Department of Medical Genetics, National Institute of Health, Rabat, Morocco.
authors.forename: A
authors.initials: A
authors.lastname: Sefiani
authors.affiliation: Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark.
authors.forename: G S
authors.initials: GS
authors.lastname: Bak
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Hove
authors.affiliation: Department of Paediatrics, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
authors.forename: L K
authors.initials: LK
authors.lastname: Hansen
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: C R
authors.initials: CR
authors.lastname: Fagerberg
authors.affiliation: Human Genomics Center, Faculty of Medicine and Pharmacy of Rabat, Rabat, Morocco.|Department of Medical Genetics, National Institute of Health, Rabat, Morocco.
authors.forename: M
authors.initials: M
authors.lastname: Tajir
authors.affiliation: Clinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: A O M
authors.initials: AO
authors.lastname: Wilkie
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000235:genetics* / Q000503:physiopathology; D009030:Mosaicism; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy
chemical_list: D004268:DNA-Binding Proteins; C000592373:ZSWIM6 protein, human
keywords: ZSWIM6; frontonasal malformation; mosaicism; preaxial polydactyly