More than 1000 variants of the ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene have been reported in neonatal diabetes mellitus. Up to now only 55 ABCC8 variants were associated with Maturity-Onset Diabetes of the Young 12 (MODY12). We present a c.3544C>T p.(Arg1182Trp) ABCC8 variant in a 35-year-old women who had pronounced microvascular diabetic complications and a charcot arthropathy necessitating a lower limb amputation. The unusual severity of the disease course prompted us to perform a systematic review of all genetic variants in MODY12. The present mutation has mostly been associated with neonatal diabetes and in only three papers reporting a MODY12. The 55 MODY12 variants show a large clinical heterogeneity, even in relatives with the same mutation, ranging from mild impaired glucose tolerance to severe insulin-dependent diabetes mellitus. HbA1c at diagnosis ranged from 5% to 14% and age at diagnosis ranged from 2 to 53 years. However, several case reports lack documentation of diabetic complications. Hence, more detailed reports remain necessary to improve insight in MODY12 pathophysiology and outcome. In this article current data regarding therapeutic management are provided, and key points to consider for the individual patient affected by MODY12 are presented.

中文翻译：

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MODY12中的ABCC8变体：严重并发症病例的文献回顾和报告

在新生儿糖尿病中报告了超过 1000 种 ATP 结合盒转运蛋白亚家族 C 成员 8 (ABCC8) 基因的变体。到目前为止，只有 55 个 ABCC8 变体与青少年 12 岁成人糖尿病 (MODY12) 相关。我们在一名 35 岁的女性中提出了 c.3544C>T p.(Arg1182Trp) ABCC8 变体，该女性患有明显的微血管糖尿病并发症和需要截肢的 charcot 关节病。疾病过程的异常严重性促使我们对 MODY12 中的所有遗传变异进行系统审查。目前的突变主要与新生儿糖尿病有关，并且仅在三篇报告 MODY12 的论文中。55 个 MODY12 变体显示出很大的临床异质性，即使在具有相同突变的亲属中，从轻度糖耐量受损到严重的胰岛素依赖型糖尿病。诊断时的 HbA1c 范围为 5% 至 14%，诊断时的年龄范围为 2 至 53 岁。然而，一些病例报告缺乏糖尿病并发症的记录。因此，仍然需要更详细的报告来提高对 MODY12 病理生理学和结果的认识。本文提供了有关治疗管理的当前数据，并介绍了受 MODY12 影响的个体患者需要考虑的关键点。