A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy

被引:149
作者
Caux, F
Dubosclard, E
Lascols, O
Buendia, B
Chazouillères, O
Cohen, A
Courvalin, JC
Laroche, L
Capeau, J
Vigouroux, C
Christin-Maitre, S
机构
[1] Hop Avicenne, Dermatol Serv, F-93000 Bobigny, France
[2] Inst Jacques Monod, Dept Biol Cellulaire, UMR 7592, F-75005 Paris, France
[3] Univ Paris 13, UPRES EA3408, F-93430 Villetaneuse, France
[4] Hop St Antoine, INSERM, U402, Fac Med St Antoine, F-75012 Paris, France
[5] Hop St Antoine, Mol Biol Lab, Federat Biochim, F-75012 Paris, France
[6] Hop St Antoine, Serv Hepatol, F-75012 Paris, France
[7] Hop St Antoine, Serv Cardiol, F-75012 Paris, France
[8] Hop St Antoine, Serv Endocrinol, EA 1533 Genet Reprod Humaine, F-75012 Paris, France
关键词
D O I
10.1210/jc.2002-021506
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A-Type lamins, arising from the LMNA gene, are intermediate filaments proteins that belong to the lamina, a ubiquitous nuclear network. Naturally occurring mutations in these proteins have been shown to be responsible for several distinct diseases that display skeletal and/or cardiac muscle or peripheral nerve involvement. These include familial partial lipodystrophy of the Dunnigan type and the mandibuloacral dysplasia syndrome. The pathophysiology of this group of diseases, often referred to as laminopathies, remains elusive. We report a new condition in a 30-yr-old man exhibiting a previously undescribed heterozygous R133L LMNA mutation. His phenotype associated generalized acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, hepatic steatosis, hypertrophic cardiomyopathy with valvular involvement, and disseminated whitish papules. Immunofluorescence microscopic analysis of the patient's cultured skin fibroblasts revealed nuclear disorganization and abnormal distribution of A-type lamins, similar to that observed in patients harboring other LMNA mutations. This observation broadens the clinical spectrum of laminopathies, pointing out the clinical variability of lipodystrophy and the unreported possibility of hypertrophic cardiomyopathy and skin involvement. It emphasizes the fact that the diagnosis of genetic alterations in A-type lamins requires careful and complete clinical and morphological investigations in patients regardless of the presenting signs.
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收藏
页码:1006 / 1013
页数:8
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