van der Vorm E R, Kuipers A, Bonenkamp J W, Kleijer W J, Van Maldergem L, Herwig J, Maassen J A
Department of Medical Biochemistry, Sylvius Laboratories, State University, Leiden, The Netherlands.
Diabetologia. 1993 Feb;36(2):172-4. doi: 10.1007/BF00400701.
Lipodystrophic diabetes mellitus of the Seip-Berardinelli type is a syndrome associated with insulin resistance and recessive inheritance. We have examined whether mutations in the insulin receptor are pathogenetic factors in this syndrome. Fibroblasts from three different patients with Seip-Berardinelli's lipodystrophy were tested for insulin binding, and insulin-stimulated receptor autophosphorylation. In addition, the coding region of both alleles of the iinsulin receptor gene was sequenced. No abnormalities in the number of high affinity insulin binding sites, and insulin-stimulated receptor autophosphorylation were detected. The insulin receptor related insulin-like growth factor I receptor also showed no functional changes. DNA sequence analysis of the amplified exons of the insulin receptor gene showed a silent mutation in patient 1 at codon Ser339, changing AGT to AGC. In patient 2 a heterozygous Met for Val substitution at position 985 was detected, which is a rare polymorphism. In patient 3 no mutations, other than described polymorphisms, were observed. These findings demonstrate that the primary genetic lesion in Seip-Berardinelli's lipodystrophy is outside the insulin receptor gene and that an involvement of the insulin-like growth factor I receptor is also unlikely.
塞普-贝拉尔迪内利型脂肪营养不良性糖尿病是一种与胰岛素抵抗和隐性遗传相关的综合征。我们研究了胰岛素受体突变是否是该综合征的致病因素。对三名不同的塞普-贝拉尔迪内利脂肪营养不良患者的成纤维细胞进行了胰岛素结合和胰岛素刺激的受体自身磷酸化检测。此外，对胰岛素受体基因两个等位基因的编码区进行了测序。未检测到高亲和力胰岛素结合位点数量及胰岛素刺激的受体自身磷酸化存在异常。胰岛素受体相关的胰岛素样生长因子I受体也未显示功能变化。对胰岛素受体基因扩增外显子的DNA序列分析显示，患者1在密码子Ser339处存在沉默突变，AGT变为AGC。在患者2中检测到第985位存在杂合的甲硫氨酸替代缬氨酸，这是一种罕见的多态性。在患者3中，除了所述的多态性外，未观察到其他突变。这些发现表明，塞普-贝拉尔迪内利脂肪营养不良的主要遗传病变在胰岛素受体基因之外，且胰岛素样生长因子I受体也不太可能参与其中。
