Abbott Megan, Angione Katie, Forbes Emily, Stoecker Mikayla, Saenz Margarita, Neul Jeffrey L, Marsh Eric D, Skinner Steven A, Percy Alan K, Benke Tim A
Department of Child Neurology, Children's Hospital Colorado, Aurora, Colorado, USA.
School of Medicine, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado, USA.
Am J Med Genet A. 2024 Oct;194(10):e63725. doi: 10.1002/ajmg.a.63725. Epub 2024 May 22.
Typical (or classic) Rett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by a period of regression, partial or complete loss of purposeful hand movements, and acquired speech, impaired gait, and stereotyped hand movements. In over 95% of typical RTT, a pathogenic variant is found in the methyl-CPG binding protein 2 gene (MECP2). Here, we describe a young woman with clinically diagnosed typical RTT syndrome who lacked a genetic diagnosis despite 20 years of investigation and multiple rounds of sequencing the MECP2 gene. Recently, additional genetic testing using next-generation sequencing was completed, which revealed a partial insertion of the BCL11A gene within exon 4 of MECP2, resulting in a small deletion in MECP2, causing likely disruption of MeCP2 function due to a frameshift. This case demonstrates the ever-changing limitations of genetic testing, as well as the importance of continual pursuit of a diagnosis as technologies improve and are more widely utilized.
典型（或经典）雷特综合征（RTT）是一种X连锁神经发育障碍，其特征为一段发育倒退期、有目的手部动作部分或完全丧失、后天获得性语言能力受损、步态障碍以及刻板手部动作。在超过95%的典型RTT病例中，甲基化CpG结合蛋白2基因（MECP2）存在致病变异。在此，我们描述一名临床诊断为典型RTT综合征的年轻女性，尽管经过20年的调查以及多轮MECP2基因测序，仍未获得基因诊断结果。最近，利用二代测序技术完成的进一步基因检测显示，BCL11A基因部分插入到MECP2基因的第4外显子内，导致MECP2出现小片段缺失，可能因移码而破坏MeCP2功能。该病例表明基因检测的局限性不断变化，同时也凸显了随着技术进步和更广泛应用，持续追求诊断的重要性。
