Abstract：
Activity-dependent neuroprotective protein (ADNP) is essential for neurodevelopment and de novo mutations in ADNP cause the ADNP syndrome. From brain pathologies point of view, tauopathy has been demonstrated at a young age, implying stunted development coupled with early/accelerated neurodegeneration. Given potential genotype-phenotype differences and age-dependency, we have assessed here a cohort of 15 individuals (1-27-year-old), using 1-3 longitudinal parent (caretaker) interview/s (Vineland 3 questionnaire) over several years. Our results indicated developmental delays, or even developmental arrests, coupled with potential spurts of development at early ages. Severe outcomes correlated with the truncating high impact mutation, in other words, the remaining mutated protein length as well as with the tested individual age, corroborating the hypothesis of developmental delays coupled with accelerated aging. A significant correlation was noted between mutated protein length and communication, implying a high impact of ADNP on communicative skills. Additionally, correlations were discovered between the two previously described epi-genetic signatures in ADNP emphasizing aberrant acquisition of motor behaviors, with truncating mutations around the nuclear localization signal being mostly affected. Finally, all individuals seem to acquire an age equivalent of 1-6 years, requiring disease modification treatment, such as the ADNP-derived drug candidate, NAP (davunetide), which has recently shown efficacy in women suffering from the neurodegenerative disorder, progressive supranuclear palsy (PSP), a late-onset tauopathy.
摘要：
活性依赖性神经保护蛋白（ADNP）对神经发育至关重要，ADNP中的从头突变会导致ADNP综合征。从脑病理学的角度来看，在年轻的时候就已经证明了tau蛋白病，暗示发育迟缓与早期/加速的神经变性。鉴于潜在的基因型-表型差异和年龄依赖性，我们在这里评估了一组15人(1-27岁)，在几年内使用1-3个纵向家长(看守)访谈(Vineland3问卷)。我们的结果表明发育迟缓，甚至是发展性逮捕，再加上早期发育的潜在突增。严重结局与截断高影响突变相关，换句话说,剩余的突变蛋白长度以及测试个体的年龄，证实了发育迟缓与加速衰老的假设。突变的蛋白质长度和通讯之间存在显着相关性，这意味着ADNP对交际技能的影响很大。此外,在ADNP中的两个先前描述的表观遗传特征之间发现了相关性，强调了运动行为的异常获得，核定位信号周围的截断突变主要受到影响。最后,所有的人似乎都获得了相当于1-6岁的年龄，需要疾病改良治疗，例如ADNP衍生的候选药物，NAP(davunetide),最近在患有神经退行性疾病的女性中显示出疗效，进行性核上性麻痹（PSP），迟发性tau蛋白病.
