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: Adeline Jacquinet, Alain Verloes, Bert Callewaert, Christine Coremans, Paul Coucke, Anne de Paepe, Uwe Kornak, Frederic Lebrun, Jacques Lombet, Gérald E Piérard, Peter N Robinson, Sofie Symoens, Lionel Van Maldergem, François-Guillaume Debray
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 57 Issue 5 Pg. 230-4 (Apr 2014) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 24613577 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• FBN1 protein, human
• Fibrillin-1
• Fibrillins
• Microfilament Proteins

Topics

• Adolescent
• Amino Acid Sequence
• Base Sequence
• DNA Mutational Analysis
• Diagnosis, Differential
• Female
• Fetal Growth Retardation (diagnosis, genetics)
• Fibrillin-1
• Fibrillins
• Humans
• Lipodystrophy (congenital, diagnosis, genetics)
• Marfan Syndrome (diagnosis, genetics)
• Microfilament Proteins (genetics)
• Molecular Diagnostic Techniques
• Molecular Sequence Data
• Progeria (diagnosis, genetics)