University of Basel, Biozentrum, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
University of Basel, Biozentrum, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland; Kantonsspital Baden, Clinical Trial Unit, Im Ergel 1, CH-5405 Baden, Switzerland.
Best Pract Res Clin Endocrinol Metab. 2020 Sep;34(5):101432. doi: 10.1016/j.beem.2020.101432. Epub 2020 Jun 19.
In the majority of cases, hereditary neurohypophyseal diabetes insipidus (DI) is a monogenic disorder caused by mutations in the AVP gene. Dominant transmission is by far the most common form. In these patients, symptoms develop gradually at various ages during childhood, progressing with complete penetrance to polyuria and polydipsia that is usually severe. In autosomal dominant neurohypophyseal DI (ADNDI), the mutant prohormone is folding deficient and consequently retained in the ER, where it forms amyloid-like fibrillar aggregates. Degradation by proteasomes occurs, but their clearance capacity appears to be insufficient. Postmortem studies in affected individuals suggest a neurodegenerative process confined to vasopressinergic neurons. Other forms of genetic neurohypophyseal DI include the very rare autosomal recessive type, also caused by mutations in the AVP gene, and complex multiorgan disorders, such as Wolfram syndrome. In all individuals where a congenital form of DI is suspected, including nephrogenic types, genetic analysis should be performed.
在大多数情况下，遗传性神经垂体性尿崩症（DI）是一种由 AVP 基因突变引起的单基因疾病。显性遗传是最常见的形式。在这些患者中，症状在儿童期的不同年龄逐渐出现，完全穿透性地进展为多尿和多饮，通常很严重。在常染色体显性遗传性神经垂体 DI（ADNDI）中，突变前激素折叠缺陷，因此在 ER 中保留，在 ER 中形成类淀粉样纤维状聚集物。通过蛋白酶体进行降解，但它们的清除能力似乎不足。对受影响个体的尸检研究表明，存在局限于血管加压素能神经元的神经退行性过程。其他形式的遗传性神经垂体 DI 包括非常罕见的常染色体隐性遗传型，也由 AVP 基因突变引起，以及复杂的多器官疾病，如 Wolfram 综合征。在所有怀疑患有先天性 DI 的个体中，包括肾源性类型，都应进行基因分析。
