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

2014; Elsevier BV; Volume: 57; Issue: 5 Linguagem: Inglês

10.1016/j.ejmg.2014.02.012

1878-0849

Adeline Jacquinet, Alain Verloès, Bert Callewaert, Christine Coremans, Paul Coucke, Anne De Paepe, Uwe Kornak, Frédéric Lebrun, Jacques Lombet, Gérald Pierard, Peter N. Robinson, Sofie Symoens, Lionel Van Maldergem, François‐Guillaume Debray,

Nuclear Structure and Function

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.