Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3 %26apos; end of FBN1 gene

作者：Jacquinet Adeline; Verloes Alain; Callewaert Bert; Coremans Christine; Coucke Paul; de Paepe Anne; Kornak Uwe; Lebrun Frederic; Lombet Jacques; Pierard Gerald E; Robinson Peter N; Symoens Sofie; Van Maldergem Lionel; Debray Francois Guillaume^*

来源：European Journal of Medical Genetics, 2014, 57(5): 230-234.

DOI：10.1016/j.ejmg.2014.02.012

• Congenital lipodystrophy
• Neonatal progeria
• Marfanoid features
• Fibrillinopathy

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%26gt;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%26apos; end of FBN1. This syndrome should be considered in differential diagnosis of neonatal progeroid syndromes.

• 出版日期2014-4
• 单位河北医科大学