title: Strømme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF.
abstract: Strømme syndrome was first described by Strømme et al. (1993) in siblings presenting with "apple peel" type intestinal atresia, ocular anomalies and microcephaly. The etiology remains unknown to date. We describe the long-term clinical follow-up data for the original pair of siblings as well as two previously unreported siblings with a severe phenotype overlapping that of the Strømme syndrome including fetal autopsy results. Using family-based whole-exome sequencing, we identified truncating mutations in the centrosome gene CENPF in the two nonconsanguineous Caucasian sibling pairs. Compound heterozygous inheritance was confirmed in both families. Recently, mutations in this gene were shown to cause a fetal lethal phenotype, the phenotype and functional data being compatible with a human ciliopathy [Waters et al., 2015]. We show for the first time that Strømme syndrome is an autosomal-recessive disease caused by mutations in CENPF that can result in a wide phenotypic spectrum.
authors.affiliation: Medical Genetics, University Hospital Basel, Basel, Switzerland.
authors.forename: Isabel
authors.initials: I
authors.lastname: Filges
authors.affiliation: Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bruder
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Brandal
authors.affiliation: Medical Genetics, University Hospital Basel, Basel, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Meier
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Dag Erik
authors.initials: DE
authors.lastname: Undlien
authors.affiliation: Section of Paediatric Neurohabilitation, Department of Clinical Neurosciences for Children, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Trine Rygvold
authors.initials: TR
authors.lastname: Waage
authors.affiliation: Obstetrics and Gynecology, University Hospital Basel, Basel, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Hoesli
authors.affiliation: Institute for Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Schubach
authors.affiliation: Biozentrum and Swiss Institute of Bioinformatics, University of Basel, Basel, Switzerland.
authors.forename: Tjaart
authors.initials: T
authors.lastname: de Beer
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hoeller
authors.affiliation: Neonatology, University Children's Hospital Basel, Basel, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Schulzke
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Oddveig
authors.initials: O
authors.lastname: Røsby
authors.affiliation: Medical Genetics, University Hospital Basel, Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Miny
authors.affiliation: Centre for Prenatal Ultrasound, Basel, Switzerland.
authors.forename: Sevgi
authors.initials: S
authors.lastname: Tercanli
authors.affiliation: Department of Ophthalmology, Section for Pediatric Ophthalmology, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Truls
authors.initials: T
authors.lastname: Oppedal
authors.affiliation: Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Meyer
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Kaja Kristine
authors.initials: KK
authors.lastname: Selmer
authors.affiliation: Section for Clinical Neurosciences, Department of Pediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Petter
authors.initials: P
authors.lastname: Strømme
mesh_terms: D000328:Adult; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D000072661:Ciliopathies / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D005260:Female; D005500:Follow-Up Studies; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D007409:Intestinal Atresia / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D035781:Siblings; D055815:Young Adult
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D008840:Microfilament Proteins; C094772:centromere protein F
keywords: CENPF; Strømme syndrome; ciliopathy; fetal autopsy; intestinal atresia