title: Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene.
abstract: We report a 16-year-old girl with neonatal progeroid features and congenital lipodystrophy who was considered at birth as a possible variant of Wiedemann-Rautenstrauch syndrome. The emergence of additional clinical signs (marfanoid habitus, severe myopia and dilatation of the aortic bulb) lead to consider the diagnosis of the progeroid variant of Marfan syndrome. A de novo donor splice-site mutation (c.8226+1G>A) was identified in FBN1. We show that this mutation leads to exon 64 skipping and to the production of a stable mRNA that should allow synthesis of a truncated profibrillin-1, in which the C-terminal furin cleavage site is altered. FBN1 mutations associated with a similar phenotype have only been reported in four other patients. We confirm the correlation between marfanoid phenotype with congenital lipodystrophy and neonatal progeroid features (marfanoid-progeroid-lipodystrophy syndrome) and frameshift mutations at the 3' end of FBN1. This syndrome should be considered in differential diagnosis of neonatal progeroid syndromes.
authors.affiliation: Department of Medical Genetics, CHU and University of Liège, Liège, Belgium.
authors.forename: Adeline
authors.initials: A
authors.lastname: Jacquinet
authors.affiliation: Department of Medical Genetics and INSERM U676, APHP-Robert Debré University Hospital, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.affiliation: Center for Human Genetics, Gent UZ Hospital, Gent, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Callewaert
authors.affiliation: Pediatric Department, Clinique de l'Espérance, Liège, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Coremans
authors.affiliation: Center for Human Genetics, Gent UZ Hospital, Gent, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Coucke
authors.affiliation: Center for Human Genetics, Gent UZ Hospital, Gent, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: de Paepe
authors.affiliation: Institute of Medical Genetics and Human Genetics, Charité-Universitaetsmedizin Berlin, Berlin, Germany; Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Kornak
authors.affiliation: Pediatric Department, Clinique de l'Espérance, Liège, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Lebrun
authors.affiliation: Pediatric Department, CHR Citadelle, Liège, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Lombet
authors.affiliation: Department of Dermatopathology, CHU and University of Liège, Liège, Belgium.
authors.forename: Gérald E
authors.initials: GE
authors.lastname: Piérard
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany; Berlin-Brandenburg Centre for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
authors.affiliation: Center for Human Genetics, Gent UZ Hospital, Gent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Symoens
authors.affiliation: Center for Human Genetics, Université de Franche-Comté, Besançon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Van Maldergem
authors.affiliation: Department of Medical Genetics, CHU and University of Liège, Liège, Belgium; Pediatric Department, Clinique de l'Espérance, Liège, Belgium. Electronic address: fg.debray@chu.ulg.ac.be.
authors.forename: François-Guillaume
authors.initials: FG
authors.lastname: Debray
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis* / Q000235:genetics; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008060:Lipodystrophy / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics*; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D011371:Progeria / Q000175:diagnosis* / Q000235:genetics; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: Congenital lipodystrophy; Fibrillinopathy; Marfanoïd features; Neonatal progeria