J Clin Invest. 2023 Jul 17;133(14):e171499. doi: 10.1172/JCI171499.
hnRNPH2-related neurodevelopmental disorder (NDD) is caused by mutations in the HNRNPH2 gene and is associated with substantial challenges, including developmental delay, intellectual disability, growth delay, and epilepsy. There is currently no therapeutic intervention available to those with hnRNPH2-related NDD that addresses its underlying mechanisms. In this issue of the JCI, Korff et al. studied specific gain-of-function mutations associated with hnRNPH2-related NDD, with the help of mouse models that recapitulate key features of the condition in humans. Their work paves the way for therapeutic approaches that aim to reduce the expression of mutant hnRNPH2 and highlights a role for disrupted RNA granules in neurodevelopmental and neurodegenerative disorders.
hnRNPH2 相关神经发育障碍（NDD）是由 HNRNPH2 基因突变引起的，与包括发育迟缓、智力残疾、生长迟缓以及癫痫在内的诸多重大挑战相关。目前针对 hnRNPH2 相关 NDD 患者，尚无任何能够针对其根本发病机制的治疗干预措施。在本期 JCI 中，Korff 等人在能够重现人类疾病关键特征的小鼠模型的帮助下，研究了与 hnRNPH2 相关 NDD 相关的特定功能获得性突变。他们的工作为旨在降低突变 hnRNPH2 表达的治疗方法铺平了道路，并强调了 RNA 颗粒紊乱在神经发育和神经退行性疾病中的作用。
