Phenotypic heterogeneity in patients with familial partial lipodystrophy (Dunnigan variety) related to the site of missense mutations in lamin A/C gene
Phenotypic heterogeneity in patients with familial partial lipodystrophy (Dunnigan variety) related to the site of missense mutations in lamin A/C gene
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DOI：
10.1210/jc.86.1.59
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发表时间：
2001-01-01
影响因子：
5.8
通讯作者：
Bowcock, AM
中科院分区：
文献类型：
--
作者：
Garg, A;Vinaitheerthan, M;Bowcock, AM
层蛋白A/C(lamin A/C，LMNA)基因在家族性部分性脂营养不良中发生突变。在12个典型FPLD家系中发现LMNA外显子8(R482Q、R482W和G465D)突变，在1个非典型家系中发现LMNA外显子11(R582H)突变。为了研究表型的异质性，我们使用人体测量和全身磁共振成像比较了患有非典型和典型FPLD的女性的体脂分布和代谢参数。与患有典型FPLD的女性相比，患有非典型FPLD的两姐妹四肢和躯干的sc脂肪损失不那么严重。尤其是从臀部和大腿近端的内侧部分。这两种类型在颈部、面部、腹内和肌肉间有相似的脂肪沉积。患有非典型FPLD的女性往往血清甘油三酯较低，而高密度脂蛋白胆固醇浓度较高。由于LMNA的外显子11不包含层蛋白C编码区的一部分，R582H突变只影响层蛋白A蛋白。因此，与典型的FPLD相比，一种独特的非典型FPLD可能是由于Lamin A与其他蛋白质和染色质的相互作用中断所致，在这种情况下，Lamin A和C的相互作用可能被破坏。
The lamin A/C (LMNA) gene has recently been reported to be mutated in familial partial lipodystrophy, Dunnigan variety (FPLD). We found mutations within exon 8 of LMNA (R482Q, R482W, and G465D) in 12 families with typical FPLD and in exon 11 (R582H) in 1 atypical family. To investigate phenotypic heterogeneity, we compared body fat distribution, using anthropometry and whole body magnetic resonance imaging, and metabolic parameters in women with atypical and typical FPLD. Compared with women with typical FPLD, the two sisters with atypical FPLD had less severe loss of sc fat from all the extremities and trunk. and particularly from the gluteal region and medial parts of proximal thighs. Both types had similar excess of fat deposition in the neck, face, intraabdominal, and intermuscular regions. Women with atypical FPLD tended to have lower serum triglyceride and higher high density lipoprotein cholesterol concentrations. As exon 11 of LMNA does not comprise part of the lamin C-coding region, the R582H mutation affects only lamin A protein. Therefore, a unique phenotype of atypical FPLD may result from disrupted interaction of lamin A with other proteins and chromatin compared with typical FPLD, in which interaction of both lamins A and C may be disrupted.