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

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• 作者：Adeline Jacquinet^a ; Alain Verloes^b ; Bert Callewaert^c ; Christine Coremans^d ; Paul Coucke^c ; Anne de Paepe^c ; Uwe Kornak^e ; ^f ; Frederic Lebrun^d ; Jacques Lombet^g ; Gé ; rald E. Pié ; rard^h ; Peter N. Robinson^f ; ⁱ ; Sofie Symoens^c ; Lionel Van Maldergem^j ; ^§ ; ; Franç ; ois-Guillaume Debray^a ; ^d ; ^§ ; ; ^{fg.debray@chu.ulg.ac.be" class="auth_mail}
• 关键词：Congenital lipodystrophy ; Neonatal progeria ; Marfanoï ; d features ; Fibrillinopathy
• 刊名：European Journal of Medical Genetics
• 出版年：April 2014
• 年：2014
• 卷：57
• 期：5
• 页码：230-234
• 全文大小：963 K

文摘

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.