UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Autism Res. 2020 Jan;13(1):11-17. doi: 10.1002/aur.2203. Epub 2019 Sep 6.
Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by mutation or deletion of the maternally inherited UBE3A allele. These pathogenic mutations lead to loss of maternal UBE3A expression in neurons. Antisense oligonucleotides and gene therapies are in development, which activate the intact but epigenetically silenced paternal UBE3A allele. Preclinical studies indicate that treating during the prenatal period could greatly reduce the severity of symptoms or prevent AS from developing. Genetic tests can detect the chromosome 15q11-q13 deletion that is the most common cause of AS. New, highly sensitive noninvasive prenatal tests that take advantage of single-cell genome sequencing technologies are expected to enter the clinic in the coming years and make early genetic diagnosis of AS more common. Efforts are needed to identify fetuses and newborns with maternal 15q11-q13 deletions and to phenotype these babies relative to neurotypical controls. Clinical and parent observations suggest AS symptoms are detectable in infants, including reports of problems with feeding and motor function. Quantitative phenotypes in the 0- to 1-year age range will permit a more rapid assessment of efficacy when future treatments are administered prenatally or shortly after birth. Although prenatal therapies are currently not available for AS, prenatal testing combined with prenatal treatment has the potential to revolutionize how clinicians detect and treat babies before they are symptomatic. This pioneering prenatal treatment path for AS will lay the foundation for treating other syndromic neurodevelopmental disorders. Autism Res 2020, 13: 11-17. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Prenatal treatment could benefit expectant parents whose babies test positive for the chromosome microdeletion that causes Angelman syndrome (AS). Prenatal treatment is predicted to have better outcomes than treating after symptoms develop and may even prevent AS altogether. This approach could generally be applied to the treatment of other syndromic neurodevelopmental disorders.
安格曼综合征（AS）是一种罕见的神经发育障碍，由母源性 UBE3A 等位基因突变或缺失引起。这些致病性突变导致神经元中母源 UBE3A 表达缺失。反义寡核苷酸和基因疗法正在开发中，这些疗法可激活完整但表观遗传沉默的父源 UBE3A 等位基因。临床前研究表明，在产前阶段进行治疗可以大大减轻症状的严重程度或防止 AS 的发生。遗传测试可以检测到 15q11-q13 染色体缺失，这是 AS 最常见的原因。新的、高度敏感的非侵入性产前测试，利用单细胞基因组测序技术，有望在未来几年进入临床，并使 AS 的早期遗传诊断更为常见。需要努力识别携带母源性 15q11-q13 缺失的胎儿和新生儿，并对这些婴儿进行表型分析，以与神经典型对照进行比较。临床和家长观察表明，AS 症状在婴儿中可被检测到，包括喂养和运动功能问题的报告。0 至 1 岁年龄范围内的定量表型将允许在未来进行产前或出生后不久进行治疗时更快速地评估疗效。尽管目前没有针对 AS 的产前治疗方法，但产前检测与产前治疗相结合，有可能彻底改变临床医生在婴儿出现症状之前检测和治疗婴儿的方式。这种针对 AS 的开创性产前治疗方法将为治疗其他综合征性神经发育障碍奠定基础。自闭症研究 2020, 13: 11-17. © 2019 自闭症国际研究协会，威利期刊，公司。 概述：对于那些婴儿染色体微缺失检测呈阳性的 AS 患儿的准父母来说，产前治疗可能会受益。产前治疗的效果预计会优于治疗症状出现后的效果，甚至可能完全预防 AS。这种方法通常可应用于其他综合征性神经发育障碍的治疗。
