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

被引：35

作者：

Jacquinet, Adeline ^{[1
,2
]}

Verloes, Alain ^{[3
,4
]}

Callewaert, Bert ^{[5
]}

Coremans, Christine ^{[6
]}

Coucke, Paul ^{[5
]}

de Paepe, Anne ^{[5
]}

Kornak, Uwe ^{[7
,8
]}

Lebrun, Frederic ^{[6
]}

Lombet, Jacques ^{[9
]}

Pierard, Gerald E. ^{[2
,10
]}

Robinson, Peter N. ^{[8
,11
]}

Symoens, Sofie ^{[5
]}

Van Maldergem, Lionel ^{[12
]}

Debray, Francois-Guillaume ^{[1
,2
,6
]}

机构：

[1] CHU, Dept Med Genet, Liege, Belgium

[2] Univ Liege, B-4000 Liege, Belgium

[3] Robert Debre Univ Hosp, AP HP, Dept Med Genet, Paris, France

[4] Robert Debre Univ Hosp, AP HP, INSERM U676, Paris, France

[5] Gent UZ Hosp, Ctr Human Genet, Ghent, Belgium

[6] Clin Esperance, Dept Pediat, Liege, Belgium

[7] Charite, Inst Med Genet & Human Genet, D-13353 Berlin, Germany

[8] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[9] CHR Citadelle, Dept Pediat, Liege, Belgium

[10] CHU, Dept Dermatopathol, Liege, Belgium

[11] Charite, Berlin Brandenburg Ctr Regenerat Therapies, D-13353 Berlin, Germany

[12] Univ Franche Comte, Ctr Human Genet, F-25030 Besancon, France

来源：

EUROPEAN JOURNAL OF MEDICAL GENETICS | 2014年 / 57卷 / 05期

关键词：

Congenital lipodystrophy; Neonatal progeria; Marfanoid features; Fibrillinopathy; DERMAL FIBROBLASTS; FIBRILLIN; FEATURES; PROFIBRILLIN; DISEASES; MATRIX; INTRON; SITE;

D O I：

10.1016/j.ejmg.2014.02.012

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：230 / 234

页数：5

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