PDF(Pubmed)
Abstract：
This case presents a somewhat unique and different phenotype of hereditary spastic paraplegia from previously reported kinase D-interacting substrate of 220 kDa (KIDINS220) gene mutation-related disease. We report a unique putative causative heterozygous mutation in KIDINS220 in a pure hereditary spastic paraplegia (HSP) patient expanding the HSP group further. We also deliberate on how our case was different from prior KIDINS220-related pathologies including spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome, and the observation of KIDINS220 and aquaporin-4 (AQP4) downregulation in the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. These findings warrant further investigations of the biology of KIDINS220. With the advent of new gene editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), variants such as ours provide an opportunity for targeted precision medicine.
摘要：
该病例与先前报道的220kDa（KIDINS220）基因突变相关疾病的激酶D相互作用底物相比，遗传性痉挛性截瘫具有某种独特且不同的表型。我们报告了在进一步扩大HSP组的纯遗传性痉挛性截瘫（HSP）患者中KIDINS220的独特推定致病杂合突变。我们还仔细研究了我们的病例与先前的KIDINS220相关病理有何不同，包括痉挛性截瘫，智力残疾,眼球震颤,和肥胖（SINO）综合征，以及特发性正常压力脑积水（iNPH）患者心室室管膜中KIDINS220和水通道蛋白4（AQP4）下调的观察。这些发现保证了对KIDINS220生物学的进一步研究。随着新的基因编辑技术的出现，如簇定期间隔短回文重复（CRISPR）/CRISPR相关蛋白9（Cas9），像我们这样的变体为有针对性的精准医学提供了机会。
