{Reference Type}: Case Reports
{Title}: Rett syndrome diagnostic odyssey: Limitations of NextGen sequencing.
{Author}: Abbott M;Angione K;Forbes E;Stoecker M;Saenz M;Neul JL;Marsh ED;Skinner SA;Percy AK;Benke TA;
{Journal}: Am J Med Genet A
{Volume}: 0
{Issue}: 0
{Year}: 2024 May 22
{Factor}: 2.578
{DOI}: 10.1002/ajmg.a.63725
{Abstract}: 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.