Department of Endocrinology, Shenzhen Hospital, Southern Medical University, Shenzhen 518100, China.
Biomed Res Int. 2021 Feb 25;2021:8878149. doi: 10.1155/2021/8878149. eCollection 2021.
Mutations in insulin receptor genes can cause severe insulin resistance syndrome. Compared with Rabson-Mendenhall Syndrome and Donohue's Syndrome, type A insulin resistance syndrome is generally not serious. The main manifestations in woman with type A insulin resistance syndrome are hyperinsulinemia, insulin resistance, acanthosis nigricans, hyperandrogenism, and polycystic ovary. . A 13-year-old girl (Han nationality) visited the hospital due to hairiness and acanthosis nigricans. Further examination revealed severe hyperinsulinemia, insulin resistance, elevated blood glucose, hyperandrogenism, and polycystic ovary. Analysis of the insulin receptor gene by sequencing showed the presence of a nucleotide change in intron 7 (c. 1610+1G > A). The mutation was a splicing mutation, which can obviously affect the mRNA splicing of the insulin receptor and cause its function loss. The patient was finally diagnosed with type A insulin resistance syndrome. After 2 months of metformin treatment, the patient had spontaneous menstrual cramps and significantly improved acanthosis nigricans and sex hormones.
We report for the first time a new splicing mutation on the insulin receptor gene at the 7th intron (c.1610+1G > A), which leads to type A insulin resistance syndrome. In clinically suspected patients with polycystic ovary syndrome, if there are extremely high blood levels of insulin in the blood, genetic testing should be performed to detect insulin receptor gene mutation of type A insulin resistance syndrome.
胰岛素受体基因的突变可导致严重的胰岛素抵抗综合征。与 Rabson-Mendenhall 综合征和 Donohue 综合征相比，A型胰岛素抵抗综合征通常不严重。A型胰岛素抵抗综合征女性患者的主要表现为高胰岛素血症、胰岛素抵抗、黑棘皮病、高雄激素血症和多囊卵巢。一位 13 岁的女孩（汉族）因多毛和黑棘皮病就诊。进一步检查显示严重的高胰岛素血症、胰岛素抵抗、血糖升高、高雄激素血症和多囊卵巢。通过测序分析胰岛素受体基因，发现 7 号内含子（c.1610+1G > A）存在核苷酸变化。该突变是一种剪接突变，可明显影响胰岛素受体的 mRNA 剪接，导致其功能丧失。该患者最终被诊断为 A 型胰岛素抵抗综合征。二甲双胍治疗 2 个月后，患者出现自发性月经来潮，黑棘皮病和性激素明显改善。
我们首次报道了 7 号内含子（c.1610+1G > A）上的胰岛素受体基因的新剪接突变，导致 A 型胰岛素抵抗综合征。在临床上疑诊为多囊卵巢综合征的患者中，如果血液中胰岛素水平极高，应进行基因检测以检测 A 型胰岛素抵抗综合征的胰岛素受体基因突变。
