Phenotypic gender differences in subjects with familial partial lipodystrophy (Dunnigan variety) due to a nuclear lamin A/C R482W mutation
Phenotypic gender differences in subjects with familial partial lipodystrophy (Dunnigan variety) due to a nuclear lamin A/C R482W mutation
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DOI：
10.1055/s-2003-38388
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发表时间：
2003-01-01
影响因子：
2.2
通讯作者：
Cabezas-Cerrato, J
中科院分区：
文献类型：
--
作者：
Araújo-Vilar, D;Loidi, L;Cabezas-Cerrato, J
患有家族性部分脂肪营养不良（FPLD）的女性受试者在青春期后出现表型特征，但男性受试者则没有。我们研究了一个因核纤层蛋白 A/C 基因突变 R482W 导致 FPLD 的西班牙家庭的人体测量、临床和代谢性别差异。对这个家庭的 14 名成员进行了基因研究。在 11 名杂合突变携带者（6 名男性，5 名女性）中，通过生物电阻抗分析评估身体成分，进行皮褶测量，并绘制血脂谱。此外，还测定了血浆葡萄糖、胰岛素和瘦素，并使用 HOMA 评估了胰岛素抵抗和 β 细胞反应。将年龄和体重指数匹配的10名健康女性和10名健康男性作为对照组。这些患者的身体成分与正常人相似。然而，与对照组相比，FPLD 女性的四肢皮肤褶皱更薄，但男性则不然。与未受影响的女性相比，受影响的女性（而非男性）表现出低瘦血症、胰岛素抵抗和β细胞高反应。无论性别如何，年轻患者的血脂状况均正常。仅在老年和超重患者中检测到 2 型糖尿病和高甘油三酯血症。总之，分子诊断使我们能够证明患有 FPLD 的女性在生命早期就存在脂肪组织和生化异常，而这种情况在受影响的男性中并未发生。
Phenotypic features appeared after puberty in female, but not male subjects with familial partial lipodystrophy (FPLD). We have studied anthropometrical, clinical, and metabolic gender differences in a Spanish family with FPLD resulting from a lamin A/C gene mutation, R482W. Genetic studies were carried out on 14 members of the family. In eleven heterozygous mutation carriers (6 men, 5 women), body composition was evaluated by bioelectric impedance analysis, skin-fold measurements were taken, and lipid profiles were drawn. Moreover, plasma glucose, insulin, and leptin were determined, and insulin resistance and beta cell response were evaluated using HOMA. Ten healthy women and 10 healthy men matched for age and body mass index were used as control group. Body composition was similar in these patients to normal people. However, skin-folds of extremities were thinner in FPLD women compared with those of control subjects, but not in men. The affected women, but not men, showed hypoleptinaemia, insulin resistance, and beta-cell hyperresponse compared with unaffected women. The lipid profile was normal in the young patients, irrespective of sex. Type 2 diabetes mellitus and hypertriglyceridaemia were detected in old and overweight patients only. In conclusion, molecular diagnosis allows us to demonstrate that women with FPLD present both adipose tissue and biochemical abnormalities early in life, and this did not happen in affected men.