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Eur J Med Genet. 2014 Apr;57(5):230-4. doi: 10.1016/j.ejmg.2014.02.012. Epub 2014 Mar 6.

Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene.

Author information

1
Department of Medical Genetics, CHU and University of Liège, Liège, Belgium.
2
Department of Medical Genetics and INSERM U676, APHP-Robert Debré University Hospital, Paris, France.
3
Center for Human Genetics, Gent UZ Hospital, Gent, Belgium.
4
Pediatric Department, Clinique de l'Espérance, Liège, Belgium.
5
Institute of Medical Genetics and Human Genetics, Charité-Universitaetsmedizin Berlin, Berlin, Germany; Max Planck Institute for Molecular Genetics, Berlin, Germany.
6
Pediatric Department, CHR Citadelle, Liège, Belgium.
7
Department of Dermatopathology, CHU and University of Liège, Liège, Belgium.
8
Max Planck Institute for Molecular Genetics, Berlin, Germany; Berlin-Brandenburg Centre for Regenerative Therapies, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
9
Center for Human Genetics, Université de Franche-Comté, Besançon, France.
10
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.

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.

KEYWORDS:

Congenital lipodystrophy; Fibrillinopathy; Marfanoïd features; Neonatal progeria

PMID:
24613577
DOI:
10.1016/j.ejmg.2014.02.012
[Indexed for MEDLINE]
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