Gene and phenotype analysis of congenital generalized lipodystrophy in Japanese: A novel homozygous nonsense mutation in seipin gene
Gene and phenotype analysis of congenital generalized lipodystrophy in Japanese: A novel homozygous nonsense mutation in seipin gene
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DOI：
10.1210/jc.2003-031211
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发表时间：
2004-05-01
影响因子：
5.8
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Ebihara, K;Kusakabe, T;Nakao, K
先天性全身性脂肪营养不良（CGL），Berardinelli-Seip综合征，是一种罕见的代谢紊乱，其特征是几乎完全缺乏脂肪组织从出生或婴儿早期。最近，编码未知功能的398个氨基酸的蛋白质的seipin和编码1-酰基-sn-甘油-3-磷酸酰基转移酶2的AGPAT 2被鉴定为CGL的致病基因。在来自欧洲和中东家庭的患者中发现了Seipin突变。AGPAT 2突变主要在非洲血统中发现。然而，没有关于这些基因在亚洲血统CGL发病机制中的信息。我们研究了来自独立家族的4名日本CGL患者的seipin和AGPAT 2的整个编码区的序列。他们的平均体脂含量为4.7 +/-0.5%，血浆瘦素水平为1.15 +/- 0.14 ng/ml。我们发现了一个新的无义突变seipin在密码子275（R275 X）。在4例CGL患者中，3例为R275 X纯合子。1例患者的所有外显子均未发现seipin突变。我们在日本患者中未发现任何AGPAT 2突变，表明AGPAT 2是日本CGL的次要致病基因（如果有的话）。这是日本人CGL基因和表型分析的首次报道。
Congenital generalized lipodystrophy (CGL), Berardinelli-Seip syndrome, is a rare metabolic disorder characterized by a near total lack of adipose tissue from birth or early infancy. Recently, seipin, encoding a 398-amino acid protein of unknown function, and AGPAT2, encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase 2, were identified as causative genes for CGL. Seipin mutations were found in patients from families originating from Europe and the Middle East. AGPAT2 mutations were found predominantly in African ancestry. However, no information is available on these genes in the pathogenesis of CGL in Asian ancestry. We examined the sequences of the entire coding region of seipin and AGPAT2 in four Japanese CGL patients from independent families. Their average body fat content was 4.7 +/- 0.5%, and the plasma leptin level was 1.15 +/- 0.14 ng/ml. We identified a novel nonsense mutation of seipin at codon 275 (R275X). Of four CGL patients, three were homozygous for R275X. No seipin mutation was found in any exon in one patient. We did not find any AGPAT2 mutations in our Japanese patients, suggesting that AGPAT2 is a minor causative gene, if any, for CGL in Japanese. This is the first report on gene and phenotype analysis of CGL in Japanese.